Abstracts of the Fifteenth International Australasian Winter Conference on Brain Research Queenstown, New Zealand, August—September 1997

I , r r t m J . Nwroscrmce. 1998, Vol. 94. pp. 93- 144 Reprints available directly from the publisher Photocopying permitted by license only

~c, 1998 OPA (Overseas Publishers Awociation) Amsterdam B.V. Published under license

under the Gordon and Breach Science Publishers imprint.

Printed in India.

Abstracts of the FIFTEENTH INTERNATIONAL

AUSTRALASIAN WINTER CONFERENCE ON BRAIN RESEARCH

QUEENSTOWN, NEW ZEALAND, AUGUST-SEPTEMBER 1997

Guest Editors GREG ANSON and JEFF WICKENS

Utiiversity of Otago

(Received 10 October 1997)

Editors’ Note

Although the presence of an el nino threatened to bring an early spring and curtail the much heralded skiing, the weather brought something for everyone. Spring-like conditions prevailed in the resort of Queenstown, while snow levels on the ski fields encouraged the skilled and nearly skilled to accept the challenge of defying gravity. The fifteenth annual Australasian Winter Conference on Brain Research attracted over 80 participants. featured a very high standard of student presentations, and co-hosted, with the New Zealand section of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, a combined symposium in honour of Professor Dick Laverty’s retirement. The combined symposium, “Drugs and the central nervous system: From experimental to human use”, reflected the conference’s traditional interdisciplinary neuroscience theme. Other topics this year focused on: Brainstem and Hypothalamus; Motor Control; Cell Biology; Neurophysiology; Forebrain: Plasticity and Function; Parkinson’s Disease; Clinical Aspects of Motor Control; Neurotoxicology; Clinical Neuropsychology; Spinal Cord Surgery; Neuropathology: Human Studies and Animal Models; and Selective Attention/Neuropsychology. Several countries were represented at the fifteenth conference and in addition to New Zealand included, Australia. Singapore, USA. England. and Scotland. This issue of the Inrernorional Journal ofNertroscience contains 83 abstracts of papers presented at the meeting. AWCBR is indebted to the New Zealand Neurological Foundation for its generous support of students who participated in the conference and to Roche Products (New Zealand) Ltd., Glaxo Wellcome (New Zealand) Ltd.. Douglas Pharmaceutical’s Ltd., Novartis (New Zealand) Ltd., Pharmaco (NZ) Ltd. and Astra New Zealand for their sponsorship.

Correspondence to Dr. J. Greg Anson or Dr. Jeff Wickens, University of Otago, P.O. Box 56, Dunedin. New Zealand.

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94 BRAIN RESEARCH CONFERENCE

Generalized Receptive Field Maps of the Bullfrog Vestibular System

M. G. PAULIN" and L. R. HOFFMANNb

"Departrwrit of %oolog~~. Csiiiwsitj. of' Otago, Dirtledin. New Zealarid; ' Victor' Goodhill Ear Ceiiter. Divisioii of Heud arid Neck Surgery.

L'CLA School of' Medicine, Lo.7 A J I ~ P ~ P S . CA USA

Vestibular neuron response properties are often described using transfer functions, which emphasise temporal or dynamical aspects of their function. In contrast, other sensory systems have been described primarily using receptive field maps. which emphasise spatial aspects of sensory coding. We show how these two approaches can be combined to provide functional maps of the peripheral vestibular system. These have the conceptual simplicity of ordinary receptive field maps a s well as the computational rigour and power of transfer function models. We have begun drawing a functional map of semicircular canal primary afferent neurons in the bullfrog. Kana catesbeiana.

The Induction of Nitric Oxide Synthase in the Medial Vestibular Nucleus and Prepositus Hypoglossi During

the Development of Vestibular Compensation in Guinea Pig

T. V. ANDERSON", A. R. MOULTON". D. R. KERR", P. F. SMITH". C. L. DARLINGTONb and A. J. SANSOMC

Depcirtr?icvit of Phiirrii~icologj:l'. School qf' Medical Scierices. Uriiversity of' Otago Medical School. Ditiiediri, New Zealarid;

hDepcrrtr,ierit o f Psjdiolog?. ailti the h'euroscicwce Research Centre. C 1 r i i w s i t j ~ of Otcigo. Duriediti, New Zealand;

cDepl)ortiwrit o f Pkarrmicology. Si,hool of' Medical Sciences. University of ' O t q o Medical School, Departriierit of Psj'chologj, arid the Neitroscience

Researc~h Coitre. L'riiwrsitj~ of' Otrigo. Diriiedin, New Zealand

Linilateral vestibular deafferentation (UVD) results in a syndrome of ocular motor and postural disorders. which disappears over time in a process of recovery known as vestibular compensation (VC). Kumerous electrophysiological studies have shown that VC is associated with a partial recovery of resting activity in the ipsilateral medial vestibular nucleus (MVN), but the underlying hiocheniical mechanisms responsible for VC remain to be elucidated. A previous study has shown that a low basal level of nitric oxide synthase (NOS) exists in the MVN of labyrinthine-intact animals: in the present study we investigated changes in the expression of KOS during the development of VC. Guinea pigs ( 1 1 = 8) received a surgical W D under fentazin anaesthesia and at I0 h ("uncompensated stage": 11 = 4) or 50h ("compensated stage"; n = 4), the) were killed by cervical dislocation and the ipsilateral and contralateral MVN and prepositus hypoglossi (PH) were dissected separately. The tissue was frozen in liquid nitrogen and later assayed for NOS enzyme activity using 'H-Arginine. NOS activity changed significantly in the ipsilateral and contralateral MVN between 10 and 50 h post-UVD ( p 0.05): however. the largest difference was a decrease in NOS activity in the contralateral MVN between 10 and 50h post-UVD ( p < 0.05). By contrast. NOS activity did not change significantly in PH during VC. It is possible that NOS changes in the MVN are related to the activation of N-methyl-D-aspartate (NMDA) receptors. which have been implicated in both the induction and maintenance of VC.

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BRAIN RESEARCH CONFERENCE 95

Progesterone Stimulation of Gabaergic Neuronal Activity in the Hypothalamus of the Estrogen-treated Ovariectomized Rat

D. R. GRATTAN and N. H. GRAHAM

Department of Anatomy and Structural Biology, and the Neuroscience Research Centre, Universitv of Otago, Dunedin, New Zealand

GABAergk neurons in the hypothalamus may mediate gonadal-steroid effects on gonadotropin- releasing hormone (GnRH) neurons. The aim of this study was to examine the specific effects of estradiol (E2) and progesterone (P) on GABAergic neuronal activity in the hypothalamus. Ovariectomized rats were implanted with a subcutaneous E2 capsule (OVX + E). Two days later, the animals were divided into three groups. At 0900 h, one group was sacrificed without further treatment, the second group received two implants containing diluent while the third received two subcutaneous P implants. The second and third groups were sacrificed at 1700 h. Neurochemical methods were used to estimate GABA turnover in microdissected brain regions. In OVX + E rats. luteinizing hormone (LH) levels in the blood were low at 0900 h, with a small surge measured at 1700 h. Progesterone treatment markedly increased the magnitude of this LH surge. GABA turnover was significantly affected in the antero-ventral preoptic nucleus (AVPN), a region that contains a large number of GnRH neurons. In OVX + E rats, there was a small decrease in GABA turnover in the afternoon compared with the morning. associated with the small rise in LH secretion. Surprisingly, progesterone treatment significantly increased GABA activity in the AVPN compared with estrogen treatment alone. We hypothesize that this observation may be related to a role for progesterone in terminating the LH surge, and limiting the surge to a single day during the reproductive cycle.

Supported in part by the Otago Medical Research Foundation, and by Lottery Health.

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Pedunculopontine Control of Hippocampal Theta Rhythm: Mapping in the Region of the Supramammillary Nucleus

N. R. SWAIN-CAMPBELL and N . McNAUGHTON

We have previously reported that there are three divergent pathways which gate hippocampal theta elicited by the Pedunculopontine Tegmental nucleus (PPT). The fibres from the region of PPT split into a dorsal projection to the region of the Superior Colliculus (SC): a ventral projection to the region of the Substantia Nigra (SN): and an intermediate projection within the core of the reticular formation (Stvain-Campbell. Forster and McNaughton, in preparation). The present study mapped ascending fibres at the level of the supramammillary nucleus (SUM) using the local anaesthetic. procaine hydrochloride (0.2 pL 0.1 gjml) in urethane anaesthetised rats ( 1.5 g kg). SUM is known to be part of a synchronising ascending system originating at Reticularis Pontis Oralis ( R P O ) (Kirk and McNaughton. 1993). We found evidence for two gating pathways. which had similar effects to those previously described. One in the area of the habenular or the stria terminalis (the fibre tract terminating in the habenular). The second pathway is in the region of the fasiculus retroflexus which is a fibre tract that flows from the habenular to the entopeduncular nucleus. A pathway urhich carries information important to hippocampal theta amplitude was also identified running close to the supramammillary nucleus (SUM). This is presumed to be cholinergic output flowing from the previously describes PPT, SN. SC circuit (Forster. Swain-Campbell and McNaughton. in preparation). No change in hippocampal theta rhythm a a s found with procaine injected directly into SUM.

The Superior Colliculus and Substantia Nigra are Relays for the Ascending Cholinergic Control of Hippocampal Theta Rhythm

G. L. FORSTER. N. R. SWAIN-CAMPBELL and N. McNAUGHTON

We have previously demonstrated that tibres arising in the pedunculopontine tegmental nucleus (PPT). gate hippocampal theta rhythm in the urethane-anaesthetised rat. Separate branches mere shown to travel to the Superior Colliculus (SC) and Substantia Nigra (SN). The present experiment aimed to determine whether these fibres terminate within the SC and SN. and whether they employ muscarinic receptors. Mapping with the local anaesthetic procaine (0.2- 0.5 111. 10”,0) in urethane-anaesthetised rats. showed that infusions into sites in the lower layers of SC resulted in the abolition of PPT-elicited hippocampal theta. suggesting the presence of PPT aiferents. Mapping with the muscarinic antagonist scopolamine (0.2-0.5 PI, 10%) within the lower layers of SC. resulted in the abolition of PPT-elicited hippocampal theta in adjacent regions to procaine effects. suggesting the presence of muscarinic acetylcholine receptors. Scopolamine infusions into the SN also abolished PPT-elicited theta rhythm. These results show that fibres arising in PPT that gate hippocampal theta rhythm travel to and make muscarinic synapses within the SN and the lower layers of SC.

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Role of the Dorsomedial Hypothalamic Nucleus in the Control of Hippocampal Theta Frequency

R. J. KYD and N. McNAUGHTON

Department of Psychology, University of Otago. Dunedin, New Zealand

The medial supramammillary nucleus (SUM) has been shown to be involved in the transduction of tonic impulses from ascending brainstem systems, to phasic theta frequency in the hippocampus. Inactivation of SUM in anaesthetised rats produced large reductions in, and even total abolition of, theta frequency elicited by brainstem stimulation. However, in freely moving rats only moderate reductions were observed further, when theta was elicited by spontaneous behaviour, SUM inactivation had no affect on theta frequency. An additional anaesthetic- sensitive nucleus was suggested to be involved in theta frequency control. We investigated the dorsomedial nucleus of the hypothalamus (DMH) for its possible role in encoding theta frequency. Linear arrays of glass cannulae were constructed for infusing 1 pl of the local anaesthetic procaine (20% wt/vol) into multiple adjacent sites in freely moving rats. Inactivation of DMH reduced theta frequency, although reductions were of a smaller magnitude than those for SUM. As the distance of injection sites increased from DMH, frequency reductions became smaller (as was previously shown for injections in SUM), implying that DMH was the site where frequency was being controlled. DMH and SUM appear to have a complementary role in the control of theta frequency.

Confirmation from the Amygdala of a Distributed Cholinergic Network Gating Hippocampal Theta Activity

N. McNAUGHTON, N. RIPANDELLI and N. SWAIN-CAMBELL

Department of Psychology and the Neuroscience Research Centre, University of Otago, Dunedin. New Zealand

Theta rhythm is a large amplitude sinusoidal EEG waveform that can be recorded from the hippocampal formation of rodents and mammals. Electrical stimulation in the pedunculopontine tegmental nucleus (PPT), has been shown to elicit hippocampal theta activity through cooperation between three collateral cholinergic outputs via reticular formation, substantia nigra (SN), and superior colliculus (SC), respectively. This suggests that the cholinergic gating of theta depends on a distributed network rather than a simple ascending pathway. PPT sends monsynaptic cholinergic efferents to a number of rostra1 areas including the amygdala. Stimulation of the amygdala can elicit cholinergically mediated theta activity. We predicted that the amygdala would also be part of the ascending cholinergic co-operative network. In the present study, hippocampal theta was elicited in urethane anaesthetized (1.5g/Kg) rats by PPT stimulation (100 Hz, 0.1 ms). Injections of the local anaesthetic procaine (0.2 pI or 0.5 pl. O.’mg/ml) and the anticholinergic scopolamine (0.2 pI or 0.5 pl, 0.1 mg/ml) successively were made in the amygdala via a double cannula. Blockade of the basolateral group, the central group, the lateral olfactory tract, the amygdalohippocampal nucleus and the conical nuclei, but neither the lateral nucleus nor posterolateral nucleus. abolished theta rhythm for several minutes without affecting its frequency or amplitude. The present study demonstrates that the amygdala is part of the co-operative cholinergic network which gates theta activity.

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BRAIK RESEARCH CONFERENCE

Bimanual Circle Drawing During Secondary Task Loading

J . J. SUMMERS". D. F. BYSOUTH-YOUNGa and W. D. BYBLOWb

.' Liniversir!. of Soutlirrn Qiieenslarid, Toowooinba, Queensland, 4350. Australia; 'Hicninii Motor Corirrol Laborator?,, Department of Sport and Exercise Science,

Cniwrsit?. of Aucklrrrid. Auckland. Neu, Zealand

Eight right-handed subjects performed bimanual circle drawing in four directions: two that were defined as symmetrical (inwards and outwards patterns). and two that were asymmetric (anti- clockwise and clockwise patterns) with respect to the temporal activity of homologous musculature. Movements were coordinated with an auditory metronome which was used to pace subjects at predetermined frequencies corresponding to transition frequency. where symmetric patterns are stable and asymmetrical patterns are unstable. and at 2/3rds transition frequency (both patterns stable). The auditory pacing was presented via tones which had either a high (1000 Hz) or low (500Hz) pitch. Subjects were asked to count the number of high pitch tones during circling. The percentage of high tones was varied between 0-70%. Although error rate on the counting task was within 1%. performance was best when: The number of high tones was least: movement frequency was slow, and when symmetric patterns were performed. The poorest tone-counting performance was observed at high loads when asymmetric patterns ivere performed at the transition frequency. Overall. circling performance was best when frequency was low: and when symmetric patterns where required. Worst circling performance was recorded when asymmetric patterns were performed at transition frequency. The right hand showed advantages in circularity but frequency variation was equal between sides. Neither circularity nor frequency variation was sensitive to secondary task load. The results support dynamic models where intrinsic dynamics show equivalence between symmetric and asymmetric patterns at low movement rates but greater stability in symmetric patterns a t high movement rates. Importantly. asymmetric pattern kinematics and stability at transition frequency impinge upon. and arc sensitike to. cognitive processing.

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Bimanual Coordination Dynamics During Pre- and Post-Perturbation Using Transcranial Magnetic Stimulation

w. D. BY BLOW^, s. WILSON~, D. MACKAY~, J. J. SUMMERS' and D. BYSOUTH-YOUNGc

aHuman Motor Control Laboratory, Department of Sport and Exercise Science, University of Auckland, Auckland, New Zealand;

bDepartment of Biology, University of Southern Queensland, Toowoomba Queensland 4350, Australia;

'Department of Psychology, University of Southern Queensland, Toowoomba, Queensland 4350, Australia

Four subjects performed wrist flexion and extension motions primarily through flexor carpi radialis (FCR) and extensor carpi radialis (ECR) involvement in unimanual conditions, and two patterns of coordination: in-phase (homologous muscles, FCR and ECR. active synchronously) and anti-phase (homologous FCR and ECR active asynchronously). Move- ments were performed in time to an auditory metronome which was used to pace subjects at pre-determined frequencies corresponding to transition frequency, where in-phase patterns are stable and anti-phase patterns are unstable, and 2/3rds transition frequency (in-phase and anti- phase patterns are stable). During twenty second trials, two applications of transcranial magnetic stimulation (TMS) were provided to illicit maximal response for FCR/ECR for either the left or right hand. Two intensities of TMS were used: 6% above threshold response, and 26% above threshold response. The overarching result was that in-phase patterns were inherently more stable than anti-phase patterns in pre and post-perturbation dynamics. There was some evidence that the dominant hand was more stable in frequency than the nondominant hand. The descending perturbation was evident on the stimulated hand trajectory as well as on the non-stimulated side implicating coupling between the hands at the corticospinal level. The results of this paper focus on recovery dynamics of descending perturbations. and the mapping of neural dynamics onto models of abstract coordination dynamics.

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I00 BRAIN RESEARCH CONFERENCE

Asymmetries in the Temporal Activity of Homologous Musculature in Bimanual Ellipse Drawing

D. F. BYSOUTH-YOUNG", J. J . SUMMERSa and W. D. BYBLOWh

"Hirimti Motor Coritrol Laborator>,, Departnient of Psyclzologj, University of Soirtlrerti Qireerislmd. Toowoor?ibu, Qiceetislarid 4350. Australia;

Huniun Motor Control Laborutorj.. Depurtment of Sport mid Esercise Science. L'niversit?. of' Aiicklatid. Airckland. New Zealatid

Eight right-handed hubjects performed bin~anual ellipse drawing in four orientations: two defined by spatial symmetry about the midline; and two defined by spatial asymmetry about the midline. Within each orientation ellipse patterns were performed in four directions: two that were defined as symmetrical with respect to the temporal activity of homologous musculature (inwards and outwards patterns). and two that were asymmetric in terms of the temporal activity of homologous musculature (anti-clockwise and clockwise patterns). Movements were coordinated with an auditory metronome a.hich was used to pace subjects a t pre-determined frequencies corresponding to transition frequency. where symmetric patterns are stable and asymmetrical patterns are unstable. and at 2 3rds transition frequency (both patterns stable). Spatially symmetric patterns were more stable than asymmetric patterns both temporally and spatially. The dominant side was better able to draw ellipses than the nondominant side and both hands were better at drawing in the preferred orientation of the mobility ellipse. Ellipse drawing in spatial and temporal asymmetric patterns frequently lost stability in either or both dimensions. with abrupt switching to symmetric patterns. In addition to temporal dynamic \tabihty. the data suggest that models of coordination should explicitly incorporate spatial symmetry when movements are expressed through effectors whose origins differ along dimensions pertaining to known anatomical and biomechanical constraints.

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The Effect of Unilateral Transcranial Magnetic Stimulation on Bilateral Coordination

S. A. WILSON“, D. MCKAY”, J. J. SUMMERSb, D. BYSOUTH-YOUNGb and W. D. BYBLOW“

“Department of Biology, University of Southern Queensland, Toowloomha, Queensland 4350, Australia;

bDepartment of Psychology, University of Southern Queensland, Toowoomba, Queensland 4350, Australia;

‘Department of Sport and Exercise Science, Universit-v of Auckland, Auckland, New Zealand

The response to suprathreshold transcranial magnetic stimulation (TMS) delivered over the motor cortex during a wrist flexion/extension movement pattern is a delay in the onset of the electromyogram (EMG) for both flexor and extensor muscles contralaterally, hence the pattern of EMG bursts associated with the movement is maintained. The delay may involve activation of cortical inhibitory fibres. To investigate the effect of this type of central perturbation on bilateral movements, TMS (6% and 26% above motor threshold) was delivered over the motor area for wrist flexor and extensor muscles of four subjects while they perfomed wrist flexion/ extension movements at pre-determined frequencies (transition frequency and 2/3 transition frequency), in time to an auditory metronome. The resulting surface EMG patterns recorded bilaterally from extensor carpi radialis and flexor carpi radialis muscles included: interruption of contralateral EMG with no ipsilateral alteration of EMG pattern; synchronisation of contralateral extensor EMG onset to the TMS with flexor muscle EMG remaining bilaterally synchronised; and delayed contralateral extensor EMG onset. In the latter two cases the time between EMG onset for the perturbed extensor muscle and its ipsilateral flexor muscle was shortened. These results will be discussed in terms of the possible neural mechanisms involved.

Functionally Stable Dynamics

P. J. TREFFNER

Department of Psychology, University of Southern Queensland, Toowoomba, Queensland 4350, Australia

The perception-action problem of actively stabilising an inherently unstable inverted pendulum is explored. Analysis of the time series of the continually changing position of the hand and angle of a rod balanced on its tip reveals multiply embedded long-term correlations between points distant in time. Such time series can be characterised as random fractal. Using the methods of rescaled-range (R/S) analysis to calculate the Hurst exponent, a fractal scaling pattern is revealed that constitutes a kind of memory for states as far as 3.5 minutes into the past. This “long-term memory” is inherent in the dynamics itself rather than explicitly coded in the connections of a neural network (although the dynamics might be embodied in such a manner). Hurst analysis also revealed a crossover point between short-term and long-term temporal correlations in the global dynamics and this point was directly related to the rod length. Thus, both extrinsic constraints (i.e., rod length) and intrinsic constraints (i.e., skill) lead to the observed behaviour. Recasting psychological properties such as “memory” in dynamicdl terms provides further evidence for level-independent, dynamical mechanisms governing cognition. Explanations in terms of dynamics also avoids the problem of somehow reconstructing phenomenological properties from presumed Aristotelian “material” causes. Instead, using dynamics, an explanation is possible that incorporates both Aristotelian “formal” causes (relating to morphology, pattern, and dynamics) and Aristotelian “final” causes (relating to teleology and task constraints). Once knowledge of the dynamics is gained. it can guide the analysis of the concomitant material causes of behaviour.

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lo? BRAIK RESEARCH CONFERENCE

Fractionated Reflex and Reaction Times in Poorly Coordinated Children

A. J. RAYNOR

School of Phj.sic,uI Ediicution. Nariwrig Technological University, Singapore

The identification of poorly coordinated (PC) children has received considerable attention in recent years. However. inl'ormation about neuromuscular factors which may contribute to the observed movement problems is lacking. To provide an insight into the status of the neuromuscular system. the patellar tendon reflex (PTR) and simple visual reaction time (RT) were fractionated and compared between poorly and normally coordinated (NC) children aged 6 - ~ 7 and 9 ~ 10 years ( i i = 40) using analysis of variance. The PTR and its components of reflex latency and motor time were not significantly affected by the level of coordination: however. the coordination by age interaction was significant ( p < 0.05) due to an increased motor time in the younger PC group. Unlike the reflexive task. the RT and its components, premotor time and motor time. were all significantly ( p < 0.05) increased in the PC group. The increased R T in PC children aupports the findings of Henderson, Rose and Henderson (1992, Jouninl of' Child P.sI~/iolo,qj~ and Psj~chicrrrj.. 33. 895 ~ 905 ). while the increased premotor time empirically supports the suggestions of Geuze and van Dellen ( 1990. Joirriiul qf'Huniaii Moveinrnt Stitdies, 19. 1 1 -24). In addition. increased motor time delays were observed under both reflexive and volitional conditions in the PC group. Together with the exaggerated patellar tendon reflex response identified by Williams and Burke ( 1995. Atlupted P/ij,siral Acrivitj @tarter/,: 12, 250 -261 J these findings indicate that the neuromuscular processing in PC children difTers to that their NC peers.

Do You React Faster if You Have to Remember What to do?

L. C. PARR-BROWNLIE". B. I. HYLAND", J. G. ANSONb and J. R. WICKENS"

' Departinerit of' Pliysiolog,r, litid the Neirroscience Research Center, C'nirersitj. of Otiigo, Diiiieiiiii. New Zealand;

bScliool of' Phj.siccil Edircatiori. and the Neirroscience Research Center. L'niyersifj. of Ofago. Duriediri. New Zealund;

Dep~irtt?it~tit of' i l m t o m j . and Strircfurol Biologj-. and the Neuroscience Research Cmter, CTiiiversitj. of Otago, Dirnedin, New Zealand

Smyrnis et 01.. reported (E.vp Braiti Res.. 1992. 92. 139- 151) that precued reaction time in monkeys was faster if the precue was memorised than when the precue was continuously available. This result was supported by neuronal population vector analysis: Memorised trials had longer population vectors during the later part of the foreperiod, presumably allowing earlier activation of agonist muscles. l n huinans. Labutta p t a/ . (Mooemenr Disorders. 1994. 9, 21 8 ~~ 222) reported similar trends but no statistical analyses were performed. The current study investigated the eEect of memorising precues on reaction times in human subjects. Reaction times were measured in I4 healthy adults (mean age = 25.0 5 4.5 years). performing a precued, 4-target, forearm supination pronation task. A nonmemorised condition in which the precue remained illuminated throughout the foreperiod (750- I050 ms) was compared with a inemorised condition in which the precue was illuminated briefly (300 ms) a t the beginning of the foreperiod. Reaction time overall was significantly faster ( p < 0.01) in the non-memorised condition than in the memorised condition. These results conflict with Smyrnis et nl. (1992) and Labutta E ( d. (1994) and might be attributed to subtle differences in foreperiod duration and/or task.

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Foreperiod Length, but not Memory, Affects Human Reaction Time in a Pre-cued, Delayed Response Task

A. A. MOHAGHEGHI”, J. G. ANSONa, B. 1. HYLANDb, L. PARR-BROWNLIE and J. R. WICKENS

“School of Physical Education, and the Neuroscience Research Centre, University of Otago, Dunedin, New Zealand:

‘Department of Physiology, and the Neuroscience Research Centre, University of Otago, Dunedin. New Zealand:

‘Department of Anatomy and Structural Biology and the Neuroscience Research Centre, University of Otago, Dunedin, New Zealand

In monkeys, reaction time has been reported to be longer in non-memorized, than in memorized, delayed response tasks (Smyrnis et al., 1992, E.rp. Brain Res., 92, 139-151). In humans, Labutta et al. (1994, Movement Disorders, 9, 218 -222) reported non-significant effects of memorization in individuals with Parkinson’s disease and a group of age/gender matched control participants. We (Parr-Brownlie et al., this volume) attempted to replicate in humans the effect reported by Smyrnis et al. (1992), but obtained the opposite result. Simple reaction time (SRT) for the non-memorized task was faster than SRT for the memorized task. In the present study we tested the effect of memorization and foreperiod duration on SRT. A separate short, ( I , 2 and 3 s) and long ( 3 , 5 and 9 s) foreperiod schedules containing blocks of memorized and non-memorized responses was used. SRT was not significantly different for memorized and non-memorized conditions. SRT was substantially shorter (64 ms) when the short foreperiod schedule was used. It is possible that the memorization effect is response specific and not a direct consequence of preparation and central information processing alone.

Slow Axonal Transport of the TCPl Chaperonin Component with Actin

J. J. BRAYa, A. YUAN”, M. J. CARDENb and A. ROOBOLb

aDepurtment of Physiology, and the Neuroscience Research Centre, University of Otago, Dunedin, New Zealand:

Department of Biosciences, University of Kent at Canterbury, Kent, UK b

The eukaryotic cytosolic chaperonin is a double doughnut shaped oligomer required to correctly fold actin and tubulin (Sternlicht et al., 1993, Proc. Natl. Acad. Sci. USA, 90. 9422 - 9426). In neurons, it is likely to be important not only for generating the native forms of these cytoskeletal proteins during their perikaryal synthesis but also for maintaining them during axonal transport, which in long axons can take weeks to months. Indeed TCP-1, a defining component of this chaperonin. enters neuritic processes and colocalizes with actin at the leading edge of nerve growth cones in cultured neuronal cell lines (Roobol A. e f al., 1995, J . Cell Sci., 108, 1477-1488). To study the interaction of TCP-1 with actin in vivo and in a situation divorced from its role in biogenesis. we pulse-labelled chicken motor neurons in the lumbar spinal cord with 35s-methionine. After 12 days the sciatic nerve was cut into 1 cm segments and soluble complexes of actin plus its binding proteins were isolated by DNase 1-affinity chromatography. Proteins separated by 2D gel electrophoresis were identified by immunoblot- ting and their radioactive content estimated by fluorography. Labelled actin binding proteins included actin depolymerizing factor, cofilin, profilin, hsc 70 and TCP-I . These findings suggest that TCP-I is cotransported with soluble actin in axons and so may play an important role in maintaining actin in the native form during its slow transport to nerve terminals.

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BRAIN RESEARCH CONFERENCE

NO Induces a Collapse of Sympathetic Growth Cones

R. G. MILLS and J. DUNNE

Drpartriiciit of' Phj.siologj,. mid the Nruroscirnce Rrseurch Centre, Ltiiwrsitj. qf Otiigo, Dirrieciiii. Nrw Zealand

Hess C [ d. (1993. .V17tflre. 366. 562-565) reported a NO-induced inhibition of neurite outgrowth tiom cultured rat dorsal root ganglia. We have found that N O also causes the collapse of\ sympathetic growth cones. Chick sympathetic chain explants were grown on poly-D-lysine coated coLerslips in a modified Leibovitr L-IS medium containing 50 ng/mL nerve growth factor. After treatment with the NO donor 3-morpholinosydnonimine (SIN-I) a t concentrations ranging from 1 pM to1 mM and for periods lasting 2 min to 1 hour. explants were fixed in 3.7")" paraformaldehyde. permeablised using acetone and 3-actin fluorescently labelled. Fifty to se\enty five growth cones were examined in each ganglia and growth cones having 3 or less short filopodia were deemed to have collapsed. In untreated tissues 20&3% ( n = 4) of growth cones were judged to be collapsed. Treatment with 1 mM SIN-I had no apparent affect a t 2min but by 5 min the percentage collapsed, 32 i 3 O / b ( n = 4). had increased significantly. With increasing time of exposure the degree of collapse continued to increase and reached a maximum of 7R * jo,b after 15min. Growth cone sensitivity to NO was determined by estimating growth cone collapse after 15 min exposure. With 1 and IOpM SIN-1 there were no signiticant differences between treated and untreated tissues. However in 100 pM SIN-1 a significantly greater percentage (44+64,b, ri = 3) of cones were found collapsed. Thus yympathetic growth cones are sensitive to NO and their growth in vivo may be influenced by the release of NO.

Establishment of a Nerve Cell Line for the Study of Activity-dependent Transcription Factors

C. J. HENDERSON and M. DRAGUNOW

Deparrnieiii of' Pliurinrccologj, arid Cliiiicui Pliurincicoiogy, School q f Meriicitie. The CSiivcrsitj. of' Aircklnnd. Private Bag 92019, Auckland, New Zealarid

Espression of inducible transcription factors ( ITFs) in ncurons can be rapidly regulated by activity and may be critical in the mechanisms underlying neuronal plasticity and survival. To investigate activity-dependent expression of ITFs we utilised a retinoic acid differentiated P19 cell line. Exposing the PI9 mouse embryonal carcinoma cell line to retinoic acid induccs differentiation into a complex cellular network. containing several phenotypically distinct cell types. including postmitotic neuron-like cells with MAP-? positive processes, which showed no staining with PCNA-I. a marker of cell division. Following 4 days of culture immunocyto- chemical staining revealed low levels of basal transcription factor expression including c-Fos. Fos-B. Krox24. KroxlO. Jun-D and c-Jun. Cyclic AMP responsive element binding protein (CREB) was present in both neuronal and nonneuronal cells. however CREB phosphorylation bvas predominantly neuronal. This model system may prove useful in the study of ITFs and their possible physiological and pathological roles.

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Changes in Electrophysiological Properties of Central Olfactory Neurons Associated with Metamorphic Adult Development

of the Sphinx Moth

A. R. MERCER^, P. KLOPPENBURG~ and J. G. HILDEBRANDb

“Department of Zoology, University of Otago, Dimedin, New Zealund, and A R L Division of Neurobiology, University of Arizona, Tucson, USA;

bARL Division of Neurobiology, University of Arizona, Tucson, USA

During metamorphic adult development of the sphinx moth, Manduca sexta, there is a significant increase in the percentage of neurons that exhibit sodium-based action potentials in primary olfactory centres (antenna1 lobes, ALs) of the brain (Mercer er al., 1997, bit. J . Neuroscience, 89, 97). We have used whole-cell patch-clamp recordings in vitro and in semi- intact brain preparations to examine changes in the biophysical properties and response characteristics of AL neurons during the development of the AL neuropil. Many cells exhibited an increase in resting membrane potential, accompanied by a decrease in cell input resistance during development. Over the same period. the action-potential waveform became shorter in duration and larger in amplitude and the density of K + currents increased significantly. Most AL neurons exhibited trains of action potentials in response to intracellular injections of depolarizing current. Whether cells exhibited spike frequency adaptation depended on the cell type and on the stage of development. Some, but not all, AL neurons exhibited rebound excitation in response to hyperpolarizing current pulses and a small subset of AL neurons exhibited bursting properties. It seems likely that the biophysical properties of different categories of AL neurons reflect their roles in vivo.

Supported by NIH grant NS-28495 (JGH) and ORG MFZB06 (ARM)

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106 BRAlN RESEARCH CONFERENCE

Potassium Channels in Striatal Projection Neurons: Computer Simulation and Electrophysiological Experiments

D. McKENZIE and J. R . WICKENS

The neostriatum is the mdjor input nucleus of the basal ganglia, a set of forebrain nuclei involved in motor control and learning. The response properties of striatal neurons are dominated by their potassium channels. Potnssiuni channels may also play a role in regulating synaptic plasticity in the striatum. but this is poorly understood. Previous work has shown that extracellular application o f the potassium channel blocker tetraethyl ammonium (TEA) facilitates the induction of long-term potentiation in the striatum. However. this effect has not been scen when potassium channels are blocked by intracellular caesium (Cs) instead of cutracellulnr TEA. We are investigating thc role of potassium channels in synaptic plasticity by a combination of computer simulation and experimental work. Previously published data from current and voltage clamp studies of spiny projection neurons were used to define the computer model. The differential effects of Cs and TEA on specific channels were simulated and compared with the responses we recorded intracellularlq from striatal neurons in rat brain slices ii7 vitro. In both the model and in experimentally studied neurons, plateau potentials could be evoked following bath application or intracellular injection of these substances. but the duration and shape of these potentials differed: TEA produced more prolonged and flatter potentials than Cs. These differences in plateau potentials might underlie the differential effects of TEA and Cs on long-term potentiation in the striaturn.

Fractal analysis of Layer 111 Pyramidal Neurones in the Visual Cortex of the Macaque Monkey

H. F. JELINEK", G. ELSTONh and M. G. P. ROSAb

Using fractal analysib. the morphological cornplcxity of basal dendritic fields was compared in wnples o f layer I l l pyramidal in the primary visual area (VI ) , the second visual area (V2). the middle temporal area (MT). the Lentral portion of the lateral interparietal area (LIPv) and cytoarchitectonic area 7a of the macaque monkey. Our results demonstrated an increase in the fractal dimension of cells from V1 to MT and LIPv. The Df values of cells in VI were not rigniticantly different from those of cells in V?. Cells in M T had more complex dendritic fields than those of VI and V:! with cells in LlPv being even more complex. Cells in area 7a had Df values that varied greatly. This increase in l>f correlates with physiological data that suggests cells extrastriate cortex to process more complex visual information.

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Separating Habit from Recollection in the Water Maze

D. K. BILKEY

Department of Psychology, University of Otago, Dunedin, New Zealand

Performance in the Morris water maze spatial memory task is usually assessed by monitoring the “latency to hidden platform location” and “time in target quadrant (TIQ)” measures in probe trials conducted with the platform removed. Since previous studies have shown that lesions of entorhinal cortex produce a dissociation between these measures, such that TIQ is impaired but latency is not, they may assess different aspects of spatial learning. It has been suggested, therefore, that the TIQ measure is more sensitive than the latency measure to lesion-induced stereotyped response patterns. Although our recent studies have shown that lesions of perirhindl cortex (PRC) in rats produced a similar dissociation between the two measures, an analysis of swim paths produced no evidence of stereotyped responding. An alternative explanation of the dissociation is: i) All animals tend to make their initial approach to the platform location using “automatic” or “habit-based” memory processing which is not dependent on the PRC. This process results in normal latency measures and is theoretically capable of generating normal TIQ scores in lesioned animals, and ii) When animals perceive that the platform is missing there is a switch to PRC-dependent memory processes such that the performance of PRC-lesioned animals is impaired (poor TIQ score). One important prediction of this hypothesis is that the TIQ performance of PRC-lesioned animals should be improved by manipulations which prevent the switch from “automatic” to PRC-dependent processing. In line with this prediction we have data which demonstrate that lesions of the rat prefrontal cortex, the putative site of the “switching mechanism”, ameliorate the TIQ deficit produced by PRC lesions.

Spatial Reference and Working Memory Deficits in Rats with Electrolytic Perirhinal Cortex Lesions

P. LIU and D. K. BILKEY

Department of Psychology and the Neuroscience Research Centre, Universit-v of Otago, P.O. Box 56, Dunedin, New Zealand

To investigate whether the role of the hippocampus in spatial information processing is dependent on its extensive reciprocal connections with perirhinal cortex, bilateral electrolytic perirhinal cortex lesioned (PRC) and sham control (SHAM) rats were trained in a radial arm maze task to test both spatial reference and working memory. In the reference memory test, one arm of the maze was baited and always located in a fixed position relative to the extramaze environment. Animals (SHAM = 12, PRC = 12) were placed at the distal end of any one o f the non-target arms and allowcd to run to the end of the target arm to obtain food reward. The number of errors made by PRC animals was significantly greater than those made by SHAM animals during initial training (8 trials per day with 30s intertrial interval). After six days of training a delay period of either 5 , 60, 120 or 240 seconds was inserted between trial four and five. The PRC animals exhibited a delay-dependent impairment in trial five performance compared to controls suggesting that there was more rapid forgetting of task-related information. In the working memory test, a second group of animals (SHAM = 12, PRC = 15) were trained on the standard radial arm maze with eight arms baited. The performance of the PRC group was markedly impaired relative to sham controls although there was an improvement in performance during training. These data suggest that the perirhinal cortex plays an important role in spatial memory processing in the rat possibly via its connections to the hippocampus.

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Rapid Increase in N-Methyl-D-Aspartate Receptor Subunit NR2B Following Long-Term Potentiation

J . M. WILLIAMS". W. P. TATE", S. E. MASON-PARKERb and W. C. ABRAHAM'

In the adult hippocampus. the .V-methyl-D-aspartatc receptor (NMDAR) complex consists of the core NRI subunit and enhancer NR?A and NR2B subunits in an unknown stoichiometry. While activation of the NhlDAR is essential for the induction of long-term potentiation (LTP), it is unknown \vhether LTP is associated with a persktent alteration in NMDAR subunit composition. To inbestigate whether such changes occur following perforant path LTP in a\cake animals. protein extracts were prepared from control and tetanized dentate gyri of adult niale Sprague-Dawley rats Omin. 2Omin. 48 h and 2 weeks after LTP induction. The extracts \\ere used in immunoblot analyses \\.it11 antibodies specific to N R 2 R . These analyses demonstrated a rapid and significant increase in expression of NR2B at 70min (ratio tetanized i o control hemisphere 3.10 h0.68. mean 2 SEM. 11 = 3) and at 48 h (1.66f0.16. ii = 6) following LTP. NR2B protein was not increased 0 min post-tetanus and had returned to baseline levels by two weeks post-tetanus. N o change in NRZB protein was detected in animals that were anaesthetized with sodium pentobarbital during LTP induction. when the stimulus was given in the presence of a competitive NMDAR antagonist or when LTP decayed rapidly. These tetanus-induced changes in NMDAR subunit composition may alter NMDAR currents and contribute to the persistence of LTP.

Supported h) the Nea Zealand Health Research Council.

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Does the Priming of LTP by Activation of Group I Metabotropic Glutamate Receptors Involve a CAMP-Mediated Cascade?

s. c. W E B B ~ , w. P. TATE", c. R. RAYMOND~ and W. C. ABRAHAMb

aDepartrnent of Biochemistry, University of Otago, Dimedin, New Zealand; bDepartinent of Psychology, University of Otago, Dunedin, New Zealand

The induction of long-term potentiation (LTP) in the CAI region of the hippocampus can be facilitated (primed) by the prior activation of metabotropic glutamate receptors (mGluRs) with 3,5-dihydroxyphenyl-glycine (DHPG), a Group I mGluR specific agonist. The priming effect may result from a cyclic AMP (CAMP) mediated cascade, as DHPG has been shown to increase cAMP levels in hippocampal slices. To test this possibility, CAI mini-slices were collected over a 10 minute timecourse in the presence or absence of a dose of DHPG (20 pM) known to prime LTP. The minislices were perfused with a phosphodiesterase inhibitor, either IBMX (100 pM) or Ro 20-1724 (20 pM), for 30 minutes prior to, and during, the DHPG administration. Cyclic AMP was extracted from the mini-slices, measured by competitive binding assay (Amersham) and the levels were expressed relative to total protein in each sample, as determined by BCA assay. No change in cAMP level was observed after administration of 20 pLM DHPG in the presence of either TBMX or Ro 20-1724. The positive control, forskolin (20 pM), as expected, produced an approximately 5-fold increase in the cAMP level. These data imply that a cAMP increase is not involved in the priming of LTP by DHPG. Priming may be mediated instead by mGluR interaction with phospholipase C resulting in activation of either protein kinase C or the phosphoinositide pathway.

Supported by the New Zealand Health Research Council.

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I10 BRAIK RESEARCH CONFEREKCE

Effects of the Substantia Nigra on Synaptic Plasticity in the Rat Striatum, In Vivo

J . N . .J . REYNOLDS and J . R. WICKENS

The mechanisms underlying learning and memory functions of the basal ganglia are incompletely understood. Synaptic plasticit). a cellular model for learning. has recently been described in corticostriatal slices. folloning high frequency stimulation (HFS) of the cerebral cortex. The plasticity is modulated b) exogenuous dopamine. The present study investigated the effects of substantia nigra stimulation on synaptic plasticity in whole animals. intracellular records were made from striatal neuron\ in urethane anaesthetised rats. Spontaneous membrane potential fluctuations betHeen it hyperpolarised "Down" state and depolariscd "Up" state were recorded. Posts)naptic potentials (PSPs) were evoked by stimulation of the cortex during the "Down" state. After a baseline period. HFS (6 trains of 50 pulses at 100 Hz) was applied to either the contralateral cortex. substantia nigra. or both in conjunction. Substantia nigra HFS alone produced long-lasting increases in PSP amplitudes (more than 20% Lifter 20 min) in the majority of neurons in the sample. Cortical HFS alone resulted in long- lasting decreases in PSP amplitudes. Simultaneous HFS of cortex and substantia nigra produced a similar long-lasting decrease in amplitudes. These results suggest that substantia n i p HFS induces long-term potentiation in the striaturn. whereas cortical HFS induces long term depression. The latter etTect predominates if both cortex and substantia nigra are stimulated simultaneously. Further work n i l1 investigate the part played by dopamine in these effects.

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Low-Frequency Stimulation Contains a Priming Phase to Facilitate the Induction of Long Term Depression

C. M. COUSSENS and W. C. ABRAHAM

Departineiit of Psychology, and the Nevroscience Research Centre, University of Otago, Dimedin, New Zealand

Long-term depression (LTD) is typically induced by a 5- 15 min low frequency stimulation (LFS). The amount of time involved during the LFS suggests that events may be occurring early in the train that increase the likelihood of LTD being induced by later stimuli. To test this possibility, transverse hippocampal slices were prepared from male Sprague-Dawley rats (1 80 - 280 g) with the stimulating and extracellular recording electrodes placed in the stratum radiatum of area CAI. Test pulses were delivered to the Schaffer collateral fibers at 0.67 Hz, at an intensity sufficient to achieve a field EPSP of 0.5 mV. We used 1 and 3 Hz LFS at a 1 .O mV field EPSP strength to induce LTD. One Hz stimulation delivered continuously for 600 pulses or 900 pulses did not induce a significant LTD of the field EPSP (-6+6%, n = 4; - 1 0 f 4 % , ti = 9, respectively). It was not until 1200 pulses were delivered (either continuously or as 2 bouts of 600 pulses separated by 10 min) before LTD was induced (-21 +4%, n = 5) LFS at 3 hz produced similar results. LFS (600 pulses) primed the pathway for at least one hour (-21 & 3%, n = 5, measured after the 2nd bout of 600 pulses). These results suggest that LTD is not incremental with each pulse of stimulation but rather requires a minimum number of pulses before LTD occurs. The mechanisms by which the initial stimulation primes LTD remains to be investigated.

Supported by the New Zealand Health Research Council

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Chlordiazepoxide Injected into the Supramammillary Nucleus Affects Behaviour and Theta Activity

During a Fixed Interval Schedule

M. A. SENIOR and N. McNAUGHTON

Depurtment o j Psychologj, mid the Neirrosciencr Research Centre, L!riiwrsitj, qf Otago, Dunedin, Nrw Zealand

The hippocampus has been proposed to mediate anxiolytic action (Gray, 1982) including effects on both active coping with threat (e.g.. exploration) and passive coping (behavioural inhibition). Injection of the anxiolytic beiizadiazepine chlodiazepoxide (CDP) into the supramammillary nucleus ( SUM) reduces the frequency of hippocampal theta elicited by brainstem stimulation but has no effect on theta or behaviour during active exploration. We tested the effect5 of SLIM CDP on behavioural inhibition in a fixed interval (FI) schedule. Forty three male Sprague-Dawley rats wcre each implanted with a subicular recording electrode. Twenty nine of these were also implanted with a SUM cannula. They were then trained on an F160s with theta activity recorded concurrently. CDP (both 5mg;kg. i .p. and 20pg in 0 . 5 ~ 1 in SUM) reduced theta frequent) and increased responding. CDP outside SUM had no effects. These results indicate that SUM may be critical for the behavioural effects of the benzodiazepines, and their effects on theta. in a task that requires behavioural inhibition rather than movement.

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Timing-Related Neuronal Activity in the Hippocampus

B. J. YOUNG and N. McNAUGHTON

Department of Psychology, and Neuroscience Research Centre, University of Otago, Dunedin, New Zealand

Lesion studies show that the hippocampus is critically involved in timing behaviour. but so far there has been little analysis of how time might be encoded. We recorded the activity of 272 CAI and CA3 neurons from rats performing on a 15 second delayed reinforcement (DRLl5) schedule, where reinforcement was contingent on responses that occurred at least 15 sec after the preceding response. The unit data were analysed using two different methods. First, each unit was subjected to an ANOVA that examined the effects of: (1) the outcome of the previous response (reward or non-reward); (2) the outcome of the current response; and (3) time. This showed that changes in unit activity were related to all aspects of the task and the firing of all but one of the units changed in relation to at least one of these three factors. Second, intercorrelations between the firing profiles of individual units demonstrated a large number of functional categories of neuron. However, the most common profile was an initial increase in unit activity at the beginning of the DRLl5 interval, followed by a gradual decrease throughout the interval. We suggest that this profile reflects temporal decay in circuits which may code details of the previous trial and which could be used to “time” the DRLl5 interval.

Supported by FRST U00413 and HRC 95/016.

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I I4 BRAIN RESEARCH CONFERENCE

External Direction and Memory in Parkinson's Disease

S. J . IVORY. R . G. KNIGHT. B. E. LONGMORE and T. CARADOC-DAVIES

It has been suggested that Parkinsonian patients exhibit impairment on memory tasks that require the use of internal. self initiated strategies (see Taylor Pt a/.. 1986). This has been an important. albeit difficult. hypothesis to investigate given that with most standard clinical tests one cannot make apriori assumptions about the level of internal and internal direction conferred by any given memory task. I n a n attempt to define more precisely the relationship between external direction and memory. a sample of subjects with idiopathic Parkinson's disease (PD: I I = 10) were assessed on a modified version of the California Verbal Learning Test (CVLT) ahich allowed for a comparison between conditions in which strong organisational strategies were present and conditions in \vhich they were not. The extent to which the subjects benefited from external direction (in the form of explicit encoding conditions and retrieval cues) b v a s determined by both recall scores and the level of semantic clustering. Results indicated that the P D subjects found it difficult to plan for the retrieval of material if it occurred in the absence of explicit encoding or external retrieval cues. When external direction was provided, however. the PI) patients were able to make use of the semantic associations within word lists which, in turn. led to memory enhancement.

Provision of External Cues and Movement Sequencing in Parkinson's Disease

M . A. ROGERS", J . G. PHlLLIPS", J . L. BRADSHAW", I). JONES" and R. A. IANSEKb

One of the functions attributed. at least in part. to the basal ganglia (BG) is motor sequencing Georgiou tv ul. ( 1994. Jotirnrrl of' Scwolog?.. Xeirrosiirgrrj, and Psychiatry. 57. 368 ~ 370) found that patients ui th Parkinson'c disease (PD) exhibited progressive slowing (sequence effect) during a serial CRT button-pressing task in which advance information cueing each movement was provided and then reduced. It \vas suggested that this reflected the reliance of P D patients on external cues in the absence of normally functioning BG. The present study employed similar methodology escept that advance information was not provided until the participant began inoving. thereby assessing ahilir?, ro irrilirr advance information. Participants were 13 patients with idiopathic PD and 13 age-matched controls. Patients showed a greater sequence effect relative to controls i n the absence of advance information. probahly reflecting P D patient's difficulty in initiating and maintaining movement without external cues. Patients and controls both exhibited a sequence effect at moderate levels of advance information. At high levels of advance information patients showed the effect but controls did not, suggesting that controls, unlike patients. were able to utilise the extra information to facilitate performance. This may rcflcct more frontal aspect\ of impairment in PD

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Bimanual Co-ordination in Parkinson's Disease

K. A. JOHNSON", R. CUNNINGTON", J. L. BRADSHAW", J. G. PHILLIPS ", M. A. ROGERS a and R. IANSEK

"Department of Psychology, Monash University, Australia; bGeriatric Neurology Research Unit, Kingston Centre, Victoria, Australia

Lesions of the SMA and Parkinson's disease (PD) (which impairs BG output) are clinically reported to cause difficulties in performing co-ordinated bimanudl movements. The supplementary motor area (SMA) and basal ganglia (BG) may be important in bimanual coordination. However, experimental observations have not been conclusive. To infer the role of the BG and the SMA in co-ordinating the two arms, this study investigated the bimanual coordination of PD patients. Sixteen PD patients and matched controls, performed a bimanual cranking task, at different speeds and phase relationships. All participants could perform a bimanual in-phase movement on a pair of cranks, at fast (2Hz) and slow (1 Hz) speeds. However, the PD patients were unable to perform the asymmetric anti-phase movement, in which rotation of the cranks differed by 180". at either speed; but instead reverted to the in- phase symmetrical movement. For PD patients, performance of the in-phase movement was more accurate and stable when an external timing cue was used; however, for anti-phase movement, the external cue accentuated the tendency for patients to revert to more symmetrical, in- phase movement. This supports suggestions that the BG-SMA system has a role in the control of bimanual movements, particularly for sequential movements which require precise timing and co-ordination between the two hands.

Motor Imagery and Movement Preparation in Parkinson's Disease

R. CUNNINGTON", K. A. JOHNSONa, J. L. BRADSHAW" and R. IANSEKb

aNeriropsychology Research Unit, Department of Psychology, Monash University, Clayton, Victoria, Australia;

bGeriatric Neurology Research Unit, Kingston Centre, Warrigal Rd, Cheltenham, Victoria, Australia

Movement-related potentials (MRPs) recorded prior to voluntary movement reveal a readiness potential, most likely reflecting cortical processes associated with motor preparation and execution. Early-stage pre-movement activity is reduced in amplitude in Parkinson's disease; however, it is not clear whether this deficit relates to preparatory or execution-related processes. It may be possible to separately examine activity relating to movement preparation and execution by recording MRPs associated with imagined movements, since motor imagery is thought to involve processes of movement preparation without the end-stage processes of movement-execution. MRPs were recorded from 14 subjects with Parkinson's disease and 10 age-matched control subjects while performing a sequential button pressing task, and while imagining performance of the same task. Movement execution-related components, arising predominantly from the primary motor cortex, were relatively unaffected in Parkinson's disease; however, motor preparatory processes. most likely involving the supplementary motor area (SMA), were reduced in amplitude and showed impaired termination following the motor response for Parkinson's disease subjects. It is suggested that the basal ganglia may normally provide the necessary cue to terminate sustained motor preparatory activity of the cortex (particularly the SMA); therefore, with impaired basal ganglia function in Parkinson's disease, preparatory-stage activity involving the SMA was impaired, while movement execution related activity was relatively unaffected.

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Effect of Oral Levodopa Treatment on Articulatory Function in Parkinson's Disease

L. M. CAHILL". B. E. MURDOCH". D. G. THEODOROS", E. J. TRIGGS' and B. G. CHARLES'

Although oral lekodopa remains the most efficacious treatment of Parkinson's disease, little is known of its eRects on speech production. The study to be reported is the first research designed to investigate simultaneously the pharmacokinetic disposition (i.e., plasma concentration) of levodopa a i th i t s clinical response using lip muscle function and perceptual measures of speech output as response variables. A total of 16 patients with Parkinson's disease participated in thc study. Lip function was quantified using a coinputerised semi-conductor lip pressure transducer slsteni. Lip function measures were recorded prior to each subject being administered oral levodopa and at approximately 0.5 hr. I . 5 hr. and 4 hr post-medication, and theexact times noted. Simultaneously with the recording of lip function. a speech sample was recorded from each subject for the purpose of a perceptual analysis of articulatory function. Two blood samples were taken from each subject at varying times during the levodopa dosage interval. and the exact time and dosage of levodopa noted. The plasma concentrations of levodopa in each sample were then measured using a rapid and robust high performance liquid chromatographic procedure with lluorescence detection. Lip function measurements were expressed as percentage changes from baseline and plotted for each individual subject against time and levodopa plasma concentrations. and the resulting slots used to determine the effects of levodopa therapy on articulatory function.

Dopaminergic Mechanisms in Positive Reinforcement: A Theoretical Review

J. R. WICKENS

Depmrtmwt of A)iutoni>. mid Strirctural Biologj?, a id the Neirroscicwce Research Cerrtre. b'tiiwrsitj. of' Otogo. Dirnedin, New Zealaiid

Positive reinforcement is a key factor in the acquisition and maintenance of behaviour. Many Pieces of eLidence implicate the midbrain dopamine neurons in the underlying mechanisms of reinforcement. In particular: the dopamine neurons are activated by unexpected food, or drink rewards; electrical stimulation of the dopamine neurons has reinforcing effects similar to those produced by natural rewards: dopamine antagonists and dopamine-depleting lesions diminish the effects of natural and electrical stimulation rewards: and many drugs preferentially abused by humans are associated with altered dopaminergic function. Thus, dopamine synapses appear to be a crucial link between reinforcing stimuli and neural systems mediating the acquired behaviours. Furthermore. dopamine modulates long-term potentiation and long-term deprcssion of synaptic responses in target areas. suggesting cellular mechanisms for long-lasting effects of reinforcement. However. several observations complicate this picture: the habits reinforced by electrical stimulation of the brain are less resistant to extinction than those reinforced by more natural rewards: the responses of the dopamine neurons during learning area related more closely to the expectation than to the actual occurrence of reinforcement; and changes in response rates can occur almost immediately after changes in the intensity of reinforcement. These observations suggest that the dopaminergic endogenous reward signal is not dircctly driven by external stimuli but is internall) generated by an adaptiLe predictor of reward. and that its relevant actions include modulating short-term activity dynamics as well as long-term synaptic plasticity.

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Effects of Amphetamine on Prepulse Inhibition of the Acoustic Startle Reflex when Previously Paired

with Prepulse Stimuli: Implications for Pre-Attentive Sensory Processing

M. T. MARTIN-IVERSON

Department of Psychology and Department of Psychiatrj~ and Behavioural Sciences, Centre for Clinical Research in Neuropsychiatry,

University of Western Australia, Nedlands. Western Australia

The acoustic startle reflex (ASR) consists of a flinch response to an abrupt stimulus that occurs in all animals tested so far. The amplitude of startle reflex can be decreased by preceding it with a subthreshold acoustic stimulus (prepulse) within a narrow time frame (5-250 ms). It has been suggested that directed attention can alter the efficacy of prepulses a t inhibiting the ASR, and that schizophrenics exhibit a deficit in the attentional modulation of prepulse inhibition. In these experiments, attention to the prepulse was modified by presenting a 5000 or 8000 Hz tone 5 dB above a background broad-band noise (65 dB) to 20 of 40 rats 1920 times over 10 days, prior to testing for prepulse inhibition with both types of tones. The results indicate that habituating animals to a prepulse increases both prepulse inhibition at long stimulus onset synchronies (SOA: 60- 120-ms), and temporal summation at shorter SOAs. Pairing tones with amphetamine selectively reduces later prepulse facilitation by paired but not unpaired prepulses a t short SOAs (5-30ms), and reduces inhibition by both prepulses a t long SOAs. The attenuation of perpulse inhibition may be an “arousal”-like effect mediated by the nucleus accumbens. and the reduction in temporal summation may reflect suppression of irrelevant responses mediated by the striatum.

Age-related Changes in Human’s Sensitivity to Reward Frequency

E. G. TRIPP and B. L. ALSOP

Department of Psychology. University of Otago, Dunedin, New Zrakind

Previous studies of reward sensitivity in younger and older participants have confounded performance with response to feedback. In the present study a signal detection paradigm was used to investigate the effects of age on sensitivity to reward frequency. Children ( M = 8 years 9 months), young adults ( M = 19 years 6 months) and older adults ( M = 76 years 11 months) completed a signal detection task which required them to discriminate two pattern types. Stimuli were presented on a video monitor and participants signalled their choice by pressing the appropriate key on a simple response panel. The distribution of rewards was asymmetric with participants receiving 75% of the rewards for correct identification of one of the two pattern types. Performance was analyzed in terms of reaction time, discriminability between sample stimuli, and response bias towards the alternative producing the more frequent reward. The children had the fastest reaction times and were the least accurate in their responses. The young adult group were best able to discriminate between the two types of patterns. These resutls are consistent with the development of motor control and sustained attention as a function of age. More interestingly, bias toward the more frequently reinforced alternative, the measure of reward sensitivity, declined progressively with age. This age related decline in reward sensitivity may be an outward expression of the decrease in striatal dopaminergic function which has been shown to occur with age.

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The Type of Reward can Affect Performance in a T-maze Following Neonatal Cocaine Exposure in Rats

S. BARRON, J. A. WILLFORD, T. M. SEGAR and L. S. HANSEN-TRENCH

This stud! was designed to assess learning and juvenile play interactions neonatal or “third trimester“ cocaine exposure using a modified /-maze. Rat pups, implanted with an intragastric cannula. were artificially reared (AR) from postnatal day (PND) 4-9 with drug added to milk and concentrated in four daily feeds to mimic a binge model of drug use. There were four treatment groups: 30 mg,kg day cocaine hydrochloride. 70ing;kglday cocaine, and AR control, and a normally reared surgery control. Juvenile offspring (PND 38 -42) were tested with either a food reward (Exp. I ) or contact with a playmate as reward (Exp. 7) in the t-maze. When subjects chose the appropriate goal box. they \vere allowed one min to either eat the food ren.ard or pla) uith thcir tveight-matched same-sex conspecific. Subjects were tested for six days with five trials each day. While no deficits in learning were observed when the reward was food. the 20 mg, kg day cocaine-exposed group showed impaired learning and altered play behavior when reward was access to a play partner. Cocaine’s effects on behavior were therefore only apparent under certain reward conditions suggesting that neonatal cocaine exposure altered the rewarding properties of pla). These findings have potential long-term implications for social development and support preliminary data suggesting that cocaine-exposed children have difficulties in social and play situations.

Supported in part by NIDA DA06039.

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Computer Assisted Analysis of Oro-motor Movements in Neurologically Impaired Adults

E. THOMPSON~, B. MURDOCH~, D. THEODOROS and P. STOKES

’Motor Speech Research Unit, Department of Speech Pathology and Audiology, The University of Queensland. and The Royal

Brisbaiie Hospital, Queensland, Australia; bMotor Speech Research Unit, Department of Speech Pathology

and Audiology, The University of Queensland, Queensland, Australia

The oro-motor movements of 10 subjects with dysarthria following cerebrovascular accident, 10 subjects with Parkinson’s Disease, and 10 age-matched normal controls were evaluated using a video analysis system form documenting and quantifying oro-facial movements. Each subject’s facial movements were video recorded while completing a number of speech and non-speech tasks including: maximum lip retraction, maximum lip rounding, alternate lip retraction and lip rounding, natural production of “EE”, natural production of “OO”, and alternate production of “00 EE”. To analyse lip displacements during the various tasks, the video recording was re- played on a video editing machine and analysed using a computerised image analysis system capable of calculating calibrated distance, area, and angle measurements. Lip movements were measured directly from the video screen using the mouse controlled cursor to identify two points and then compute the distance between the points. From these data, five proportion measures, two symmetry measures and two maintenance measures were calculated. The preliminary results of this investigation indicate that a computer assisted video analysis system is a potentially valid technique for documenting lip displacement and quantifying any reduction in the range of lip movement or degree of unilateral lip weakness in neurologically impaired subjects.

Lip and Tongue Function in Multiple Sclerosis: A Physiological Analysis

B. E. MURDOCH, T. SPENCER, D. G. THEODOROS and E. C. THOMPSON

Motor Speech Research Unit, Department of Speech Pathology and Audiologsv, The University of Queensland, Australia

A physiological analysis of the articulatory function of a group of 16 adults with multiple sclerosis (MS) was performed using lip and tongue transduction systems. Sixteen non- neurologically impaired adults, matched for age and gender, served as controls. The results of the instrumental investigations revealed that the MS speakers demonstrated patterns of tongue function that were significantly different from the control speakers. Specifically, the MS speakers were found to produce significantly reduced tongue strength, endurance and rate of repetitive movements. In addition, preclinical signs of lingual dysfunction were evident in the non-dysarthric MS group on the endurance and rate tasks. These physiological findings could account for the perceptual findings of impaired articulation and reduced intelligibility. N o lip dysfunction was found on either the physiological or perceptual assessments. The results are discussed in relation to the pathophysiology of MS.

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,4re Children with Developmental Coordination Disorder Dyspraxic?

M. MIYAHARA

Mowwient Developrwnt Clinic, School qf' Phj*sical Echcation, In iwrs i t j . c!f' Otago. Neit, Zenlurirl, Dirnedin, New Zealand

Specific developmental disorder to motor function (ICD-I 0) or developmental coordination disorder (DCD) (DSM-VI) obstructs children significantly with respect to their academic achievement and activities of daily living despite the absence of intellectual retardation or any specific neurological disorder. This condition is otherwise termed developmental dyspraxia. however. a dearth of research has assessed the praxic ability of children with DCD. The present btudy evaluated six children with DCD using the modified version of the Test of Oral and Limb Apraxia. Most children performed gestures adequately to both verbal and non-verbal commands using the proximal. distal, and oral parts of their body, in that they understood the symbolic representation of the movements. When the children did not know the meanings of the gestures. they were naturally. unable to execute them in response to a verbal command. However, two children imitated such non-habitual gestures well on a non-verbal command, whereas one did poorly especially when the gestures involved the distal part of the upper limb. The results indicated that only one out of six children with DCD was dyspraxic, and that child's dlspraxia was specific to non-symbolic gestures involving the distal part of the upper limb.

Postural Steadiness: A Contributor to Hyperactivity?

K. N. BOWEN and J. G. ANSON

School of' Plij-sicrrl Education, mid the Neitroscience Research Centre, L'niversitj, qf Otago. Ditnetliii, New Zealand

Although high activity levels are a recognised feature of hyperactivity in children, there has been little quantitative data that describes postural steadiness in this group. In this study eighteen 6 - 10 year old children who were identified as having high activity levels, were age and sex matched to a control group of volunteers. Activity levels were measured using the Conners' Rating Scales completed by both parent and teacher. Postural steadiness was measured using a force platforni. as antero-posterior force during a thirty second time period. A fifteen week intervention programme was provided for ten children selected at random from the experimental group and their matched partners in the control group. The intervention programme consisted of activities which stimulated postural mechanisms through the krstibular. proprioceptive. and tactile sensory systems. Observations occurred prior to, at the mid-point. at the end of intervention, and three months later. Preliminary results indicated that there was differences in postural steadiness between the groups. in both power spectral density, and in the time required to reach a point of relative stability following movement. Parents of children in the experimental intervention group reported a significant reduction in hyperactivity. however this observation was not confirmed by teachers.

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Proprioceptive Control of Arm Movements: Psychophysical Experiments and Computer Simulations

G. K. KERRa, N. WILLIAMS" and K. R. WALLACEb

aSchool of Hunian Movement Studies, Queensland University of Technology, Kelvin Grove, Brisbane, Australia;

bRehabilitation Institute, Montreal, Quebac, Canada

The kinematic variables of position and velocity have been proposed as essential for the proprioceptive control of goal-directed arm movements. These are known to be consiously perceived, though they are thought to be processed as separate information sources. Neural discharge from muscle spindles and cutaneous receptors has also been correlated with these variables. We have employed both psychophysical experiments and computer modelling approaches to examine how these sources of proprioceptive information may be utilised by the nervous system during movement. Psychophysical experiments have determined how arm movement trajectories are adapted to different visuomotor and anthropometric relationships. These have shown that the nervous system attempts to maintain a consistent hand trajectory via alteration in the normal sequencing of joint rotations. A second series of experiments has been designed to determine the resolution with which proprioceptive position and velocity information is perceived. Results have indicated that two components of trajectory, instantaneous position and velocity, are differentially perceived during movement. Data from these experiments have been used as a basis for modelling the output of populations of primary and secondary muscle spindle afferents within the principal arm muscles. The simulations have demonstrated that ensemble encoding of muscle spindle discharge is highly correlated with the angular position and velocity of elbow and shoulder joints in addition to the tangential hand velocity. Thus, ensemble profiles may encode kinematic parameters associated with both intrinsic (body-centred) and extrinsic (Cartesian) coordinate systems. Motor structures capable of deriving such as ensemble coding would be able to regulate movements within both coordinate frameworks and provide a means for controlling both the kinematics and dynamics of movement.

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121 BRAIK RESEARCH CONFERENCE

New Light on the Mechanism of Acamprosate, a Taurine Derivative that Prevents Relapse in Alcoholics

J. M. LITTLETON. M. AL QATARI, L. LIM and 0. BOURCHENAFA

.Although taurine deri\atives have potential pharmacological value few attempts have been made to exploit this. Acamprosate is the calcium salt of iV-acetyl homotaurine and shares some of thc cellular actions of taurine. This drug has recently completed successful clinical trials in Europe in preventing reldpse in alcohol dependent patients, perhaps by suppression of withdra\val "caning". The molecular mechanism for this is uncertain. but we found bi v i t r n that acamprosate inhihits radiotracer calcium entr) in slices and cultures of rat neocortex. This occur5 whcther calcium entrj IS induced bq glutamate or K -depolarisation and is associated w i t h protcction against NMDA receptor-mediated cxcitotoxicty iti v i ~ o . Binding studies on rat braiii membranes show potent intcractions of acamprosate with binding sites for [3H]isradipine

oltage operated calcium channels) and [3H]dizocilpine (NMDA receptors). but neither interaction is direct11 compctitivc. The functional changes in calcium entry. and some of the binding characteristics. are markedly altered b) prior chronic exposure of the animals or the cultures t o ethanol. For thc NMDA receptor. the data suggest that chronic exposure to ethanol Bz i ' i i .0 alters the subunit composition of the protein so that the functional consequences of acamprosate binding are altered. Thus acamprosate suppresses excitation-induced calcium entry. particularly when this occurs after chronic alcohol exposure. a cellular action which is compatible \vith the proposed mechanism for the therapeutic use.

This research was supported by Groupe Lipha.

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Protective Effects of ACEA 1021 and SCH23390 in (S)-MDMA Induced Neurotoxicity but not (S)-Fenfluramine Neurotoxicity

B. R. RUSSELL and R. LAVERTY

Departrnent of Pharmacology, Universitji of Otago, Dunedin, New Zealand

Male Sprague-Dawley rats (35-40 days old) were administered a glycine site specific NMDA antagonist, ACEA 1021 (4 x 30 mg/kg ip 2 hourly) or a specific D1 antagonist SCH 23390 (4 x 0.1 mg/kg ip 2 hourly) 30 minutes before (S)-MDMA (4 x 10 mg/kg ip 2 hourly). Tissue concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and where applicable. dopamine (DA) and 3.4-dihydroxyphenylacetic acid (DOPAC) were measured seven days after treatment by HPLC from micropunch samples in the striatum, frontal cortex, and hippocampus. Both drugs prevented a fall in tissue content of the respective monoamines in the striatum, frontal cortex and hippocampus usually seen after (S)-MDMA. In comparable experiments, ACEA 1021 and SCH 23390 were given in the same manner before (S)- fenfluramine (4 x 10 mg/kg ip 2 hourly). Neither drug appeared to provide a significant protective effect in the frontal cortex, hippocampus, or striatum on the 5-HT or 5-HIAA depleting effects of (S)-fenfluramine. This comparison highlights the differences between (S)- MDMA and (S)-fenfluramine neurotoxicity towards 5-HT containing neurons and implies that the respective neurotoxic mechanisms are different.

Role of Brain Nitric Oxide in (*) 3,4-Methylenedioxymethamphetamine (MDMA)-induced Neurotoxicity

Y. ZHENG and R. LAVERTY

Department of Pharmacology, Medical School, University of 0 tago, Dimedin. New Zealand

We have previously reported that inhibition of brain nitric oxide synthase (NOS) by Nd-nitro- L-arginine (L-NOARG) partially protected against long-term 5-HT depletion induced by (=k) 3.4-methylenedioxymethamphetamine (MDMA) and that brain NOS activity was significantly increased following MDMA. Since acute 5-HT release and hyperthermia induced by MDMA have been implicated in the mechanisms of MDMA neurotoxicity. we investigated if L-NOARG provided its protection via the effect of altering acute 5-HT and body temperature changes after MDMA. Male Sprague-Dawley (SD) rats were given either a single dose of MDMA (40 mg/kg, i.p.) or normal saline. Another group was injected twice with L-NOARG 16 hours and 30min before MDMA. Body temperature were measured rectally using a thermistor probe at 0.5, 1, 2,4, 6 and 24 h after administration. Rats were killed at 1 h, 6 h and 24h after MDMA. The brains were rapidly removed and dissected on dry ice. Tissue concentrations of 5-HT and 5-HIAA were determined by HPLC with electrochemical detection. The results showed that pretreatment with L-NOARG altered neither the hyperthermia, nor the acute 5-HT and 5-HIAA changes after MDMA. This indicates that L-NOARG protection does not involve body temperature or acute 5-HT release effects, and suggests a more direct involvement of NO in MDMA neurotoxicity.

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1'4 BR.AIIi RESEARCH CONFERENCE

Gymnodimine Does not Affect Evoked CA1 Responses in the Hippocampal Slice Preparation

D. M. BRIGGS and D. S. KERR

Gbmnodiiiiine i5 a novel marine biotoxin produced by the dinoflagellate Gjtnnodinirmt mikimoto; and recently identified in Iiew Zealand waters. It has been reported to be toxic to a number of organisms. Gyninodimine's chemical structure is similar to brevetoxin (PbTx). which has been shown to affect neuronal responses in the hippocampus. We hypothesised that the chemical similarities might give rise to gymnodimine effects similar to those of PbTx in the hippocampus. In the prcxnt study \ye utilised the iri i,irro hippocampal slice preparation to determine the basic properties of gyinnodimine across a number of neurophysiological variables. Slices xvere obtained from adult male Sprague-Dawley rats and maintained in a normal ACSF solution at room temperature throughout all experiments. In our hands, neither gymnodmine (I00 to 1000 nM). nor its vehicle. exerted any effect on monosynaptically evoked cutracellular CA 1 potentials. In contrast. PbTx-3 ( 100 to 200 nM) produced statistically significant reductions in population spike amplitude (mean YO change: - 3 9 + 2 u / ~ ; n = 4; 17 0.001 1. These data ahich are consistent with previous PbTx results obtained at 33°C. confirm the utilit? of this iii Y ~ V ( J preparation in the detection and analysis of the brevetoxins at I n w r temperatures. In addition, we assessed the effects of PbTx on CAI responses using a paired pulse paradigm. I n seven out of eight slices tested. PbTx-3 induced a dramatic facilitation of the second e\oked spike across a range of interstimulus intervals. However, further examination of gymnodimine using paired pulse paradigins found no apparent effect on evoked CAI responses. This latter finding is consistent with out initial observation that gymnodimine has no ef tkt no monos) naptically evoked CA 1 responses during prolonged toxin administration.

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[ 3H]-Saxitoxin Radioreceptor Binding Assay Fails to Detect Several Toxic Analogues of Saxitoxin

H. I. SABA, D. J. DE VRIES and D. S. KERR

Department of Phurrnacologji, University of Otugo, Medical School, Dunedin. New Zealand

Competitive binding of radiolabelled saxitoxin [3H]-STX to its high affinity binding site in the brain has been proposed as a useful assay for detecting saxitoxin (STX) and other paralytic shellfish poisons (PSP's) acting at site-I of the sodium channel. In the present study. this assay was assessed against STX and its analogues, as well as PSP contaminated shellfish samples. Cerebral cortex of the red deer (Cervus eluphw) was used as a synaptosomal membrane source. A standard curve was generated by displacement of [-'H]-STX from the available receptor sites tising unlabelled STX. indicating an ICso of 2 .9f0 .7 nM. An acidic aqueous extract of naturally contaminated green mussels, (site D-41, Whangaparoa) provided by the CDC/ESR (N.Z.) was also assessed in the assay. The samples were reported to contain STX-equivalents of about 310pg per lOOg tissue wet weight, by mouse bioassay and by hippocampal brain slice preparation. In contrast, the radioligand binding assay indicated a presence of only 45 pg, STX- eq/100g tissue wet weight (n = 3). Reference mixtures of STX analogues were then tested for their potency as displacing ligands at the [3H]-STX receptor site. Theoretical ['HI-STX inhibition values. calculated on the basis of mouse toxicity, were then compared with measured values derived from the assay. NeoSTX fully displaced ['HI-STX at a rate not significantly different from theoretical values. In contrast. gonyautoxins and especially C-toxins failed to displace ['HI-STX from its receptors at rates equivalent to theoretical values. Thus, it appears that the competitive radioligand binding assay fails to detect several toxic analogues of STX. Independent HPLC analyses (Cawthron Institute and CDC/ESR) indicated that the site D-41 samples were in fact richer in the more poorly detected C-toxins and gonyautoxins, which could account for the failure of the radioligand binding assay to detect the full STX-equivalents in these shellfish.

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Middle-Aged Brains: Are They More Susceptible to the Post-Concussional Syndrome than Younger Brains?

J. A. OGDEN and M. WOLFE

Some people who sustain a closed head injury (CHI) suffer from a postconcussional syndrome (PCS) for a period of weeks following their injury. Symptoms resolve within three months for most people: however some are at risk for protracted sequelae. One risk factor is old age. but how old is old’? This study tests the hypothesis that middle-aged people take longer to recover from the PCS than younger adults. Participants included four groups of nine: Two CHI groups of Older (40 to 56 yrs) and Younger (16 to 24 yrs) participants who had suffered a CHI with PCS ;It least four months previously. and two age. gender, and 1Q-matched control groups. All were assessed on a battery of neuropsychological tests of verbal and non-verbal memory. attention and concentration. speed of information processing. reaction time, and executive functions. Statistical analyses indicated that older participants did more poorly than younger participants on tests of memory. and CHI participants did more poorly than non-CHI participants on tests of reaction time and psychomotor speed. Two significant age .Y head injury interactions were found; both demonstrating that a head injury appeared to effect the performance of the younger participants more than the older participants. One explanation could be that the younger participants. who were also more likely to have suffered a sports- related head injury than the older participants. took less heed of advice to rest and return gradually to work than the older participants.

Recovery from Concussion: Professional and Non-Professional Football Players

D. GRONWALL

Rugby Union guidelines for players who have been concussed specify three weeks off the field after the first injury. no further plaj. that season after two concussions, and withdrawal from contact sports after three. With the advent of professional football an elite subgroup of players now’ exists whose livelihood could be in jeopardy if these guidelines are strictly followed. Further, coaches and team managers have a vested interest in fielding their most experienced and capable footballerc. and this and media speculation put considerable pressure on their medical officers to clear them to play. Thus, these players will be highly motivated to demonstrate that they have recovered from the injury. and might be expected to differ from amateur footballers. This paper compares a small (17 = 6 ) group of professional rugby players who wer referred for neuropsychological assessment between one and three weeks after concussion with a group ( 1 1 = 15) of amateur players tested between three and eight weeks after injury. Exactly half of the professional. and eight of the fifteen non-professional players were still significantly impaired on the Paced Auditory Serial Addition Test a t the assessment. In addition. hoth groups had players at both ends of the spectrum, and relevant Factors are examined.

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The Relation Between Matrix and Striosome Damage and Clinical Profiles in Huntington’s Disease

L. J. TIPPETT a, S. THOMAS a and R. L. M. FAULL

“Department of Psychology, The University of Auckland, Private Bag 92019, Auckland, New Zealand;

bDepartment of Anatomy, The University of Auckland, Private Bag 92019. Auckland, New Zealand

Huntington’s Disease (HD) is characterised by deficits in movement, cognition and mood, and by loss of output neurons in the straitum. Nevertheless, there is considerable variability between individuals with respect to clinical and neuropathological changes. Specifically, the brains of HD individuals vary regarding loss of receptors in the neurochemical subcompartments of the striatum. The different patterns of connectivity of these compartments led to the hypothesis that specific patterns of neural change (matrix only, striosomes only, or both) will influence the clinical profile induced by HD, such that greater mood deficits will accompany striosome damage and greater motor deficits matrix damage. In this study relevant neural analyses had already been conducted on the donated brains of 31 HD individuals who had died in the last four years: Nine had striosome damage, five had matrix damage only and 17 had damage in both compartments. A retrospective investigation of the clinical history of these individuals was undertaken with family members, using a semi-structured interview and the Clinical HD Questionnaire. At time of clinical onset, the striosome group was significantly more impaired than the matrix group on the mood index, but there was no difference between the scores of the two groups on the motor index at either point of time. Implications of these findings will be discussed.

The Effect of Treatment Variables on Cognitive Function, Mood and Social Adjustment in Patients with Pituitary Tumour

K. A. PEACE

Department of Psychological Medicine, Universitji qf Otago, Dunedin. New Zealand

Three groups of 23 patients who had been treated for pituitary tumour (transfrontal. transsphenoidal surgery, and non-surgical) and 23 healthy controls were evaluated on neuropsychological, mood, and social adjustment measures. The groups did not differ with respect of age, education level or premorbid ability, which was assessed at the upper end of average. All were free of known sources of cognitive impairment such as cerebrovascular disease. Comparsion of the four groups revealed that nearly half of the transfrontal, one third of the transsphenoidal and one quarter of the non-surgical group had three or more neuropsychological test scores below the tenth percentile compared to less than 5% of the controls. Impairments in attention, memory, and executive function were found in both surgical groups. The non-surgical patients appeared to have problems on tasks requiring high levels of cognitive processing. Surgical patients were divided into two groups and compared with respect to the effect of radiotherapy. No significant negative effects on cognitive functioning were found, however, transfrontal surgery patients who had had no radiotherapy were more impaired than other patients. This was thought to be related to radical surgery. On measures of mood and social adjustment, transsphenoidal and non-surgical patients reported mild mood disturbance and impaired social adjustment. All three groups were rated by close informants as having imparied social adjustment. suggesting that of the patients, only the transsphenoidal and non-surgical patients have accurate self-appraisal of this.

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12X BRAIN RESEARCH CONFERENCE

Disorders of Auditory Processing: A Cognitive Neuropsychological Perspective

M. POLSTER

Deyartr?irrit qf' Ps,whologj~. I'ictoria Uiiiwrsitj. . Wellingtoii. New Zralaiid

Neuropsychological disorders of auditory processing appear to occur less frequently and have been less uell investigated than disorders of visual processing. Three possible reasons for this discrepancy are presented: neuroanatomical differences between the visual and auditory systems. terminological confusions relating to auditory processing disorders. and technological Factors that have made auditor) stimuli more difficult to study than visual stimuli. Then. four disorders of auditory processing that can result from selective brain damage (cortical deafness, pure word deafness. auditory agnosia and phonagnosia) are reviewed. The prominent view in the neurological literature is that these disorders represent a continuum of severity of impairment to the auditory processing system. However, drawing an analogy to similar disorders of visual processing (cortical blindness. dyslexia. visual agnosia, and prosopagnosia) and current neuropsychological theories of visual processing suggests that the auditory system may comprised of distinct processing modules. These two theoretical positions are considered and suggestions for ways to test them are presented.

Caregiver Burden in Dementia

J . M. BURKE. B. E. LONGMORE and R. G. KNIGHT

Departriierit qf Psjdiological .lfidicirie, Dunrdiri Medical School, Drpartriierit qf' PJ!diologr. Lbiiwrsitj, of Otago, Diiiiediri. New Zealand

There is growing interest in the experience of families who care for patients with dementia. Whilst there is a vast amount of literature in the area of "caregiver burden" researchers have only recently begun t o use theoretical models of stress and coping to analyse the experience of caregivers. In the present investigation. we administered a range of neuropsychological and personalit! measures to 10 patients with Senile Dementia of the Alzheimer's type (DAT) and six patients with Multiple Sclerosis (MS) on four occasions over a two year period. All patients demonstrated clear evidence of a deterioration in functioning over time and these changes were. in turn, related to outcomes measures for caregivers, in terms of perceived level of burden. affect and coping. That the data illustrated specific circumstances of the carerpatient dyad were significant in determining outcome. emphasises the importance of incorporating both qualitative and quantitative data in describing the experience of caregiver's over time.

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Impact of Psychosurgery on Cognitive and Motor Performance in Obsessive Compulsive Disorder: A Case Study

D. M. SHEPPARD", J. L. BRADSHAW", J. V. ROSENFELDb and J. R. LLOYDb

"Neuropsycholog-y Research Unit, Monash University, Melbourne, Australia; bDepartrnent of Neurosurgery, Royal Melbourne Hospital, Melborune, Australia

The impact of psychosurgery on the cognitive functioning of treatment-resistant obsessive- compulsive disorder (OCD) is briefly reviewed, and a relevant case study reported. Three tasks examining cognitive-motor performance were used with the patient one week before and 24 weeks after a bilateral anterior cingulotomy and a bilateral anterior capsulotomy in a 49 year old man with incapacitating OCD. No significant improvment in clinical levels of OCD or depression resulted, however, the patient showed post-surgical deficits when required to change response set. The post-surgical changes in performance included a selective deficit in a reaction time task for the level that had the highest cognitive load, requiring the inhibition of inappropriate responses as well as a change of response according to the presence of additional symbols. In addition the patient showed an increased movement time when required to reprogram direction of a buttom press movement after surgery. These performance deficits may reflect changes in the functioning of the frontal lobe brought about but the surgical lesions.

The Role of the Surgeon in Cervical Spine Trauma

R. A. JOHNSTON

Consultant Neurosurgeon, Department of Neurosurgery, Institute of Neurological Sciences, Southern General Hospital, Govan Road, Galsgow, Scotland

Evolution in the management and rehabilitation of patients with cervical spine trauma has brought into much shaper focus the role played by the spinal surgeon, particularly in the early stages. Early assessment of vertebral stability is made following appropriate imaging of the cervical spine and is followed by the initial decision as to whether or not stabilisation surgery is necessary or not. If stabilisation is required it should be carried out at stage appropriate to the early management of each individual patient. There is a diverse range of spinal fixation devices now available and the subsequent need for a post-operative orthotic support will depend on the surgeon's post-operative assessment of internal stabilisation. The aims of stabilisation should be recognised as primarily the prevention of secondary spinal cord injury, the prevention of spinal deformity and late subluxation and the preservation of as many spinal motion segments as possible. Prevention of spinal cord injury, apart from the obvious effect on the patient, will avoid significant expenditure to cover that patient's long term medical care. The future for management of spinal trauma lies in centralised regional units which concentrate surgical and medical experience and into which patients are transferred within 24 hours of injury.

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Thoracic Disc Disease in Auckland Hospital

R. BOET

Deptrrtiiieiit q f ’ i2’ertro.citr,qer~~, A irch-laiid Hospital, A ircklaiid. New Zealand

Over a six year period ( 1991 ~ 1996). ten patients mith thoracic disc disease were managed in Auckland Hospital. All patients presented with motor weakness, while sensory disturbances, back pain. and urinar) symptoms were kariable. Nine of the 10 disc herniations occurred in the lower thoracic spine. Thirteen operations Lvere performed on the ten patients. five posterior, five postero-lateral and three antero-lateral. Three patients required repeat surgery. All three patients had an initial posterior procedure. Two patients had a total, and six patients had a partial recovery of neurological function. Two patients had no recovery but remained neurc~logically stable. N o patients deteriorated. Of the three patients who were dependent on presentation. two became independent and one was lost to follow up. There were four complications. Two patients had an intra-operative CSF leak. Both were repaired successfully during the same procedure. One patient developed a postoperative ileus and one a persistent pleurd effusion. both of which were managed successfully with conservative measures. It is concluded that patients with thoracic disc disease are a heterogeneous group of people, each requiring an individual approach to their problem. The literature recommends a postero-lateral or antero-lateral surgical approach to these discs. These two approaches have been used in our last six cases. the posterior approach having been discarded after early experience.

Surgical Management of Thoracic Disc Prolapse

G. R. C. HOWIE

Aitckltirid Spinal Iiistitzrtr. Aiich-laiid. New Zealand

Six cases have been treated between 1987 and 1993 with a mean age of forty four years. Five patients had thoracic disc prolapse at one level. and one at two levels. The duration of symptoms ranged from two months to fifteen years. All showed severe pain and two were paraparetic. The diagnosis was confirmed by MRI scan or myelogram. Five patients were treated bq thoracotomy and anterolateral discectomy. and one by a laminectomy. All patients showed significant improvement in their pain levels. Both patients with paralysis showed major improvement. No patients showed neurological deterioration and there were no major complications.

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The “Natural History” of Posterior Iliac Crest Bone Graft Donation in Spinal Surgery: A Prospective Analysis of the Morbidity

A. C. WRAY and P. A. ROBERTSON

Auckland Hospital, Auckland, New Zealand

Consecutive patients (n = 106) undergoing posterior iliac crest (PIC) donation of bone were studied. Data completion was 96% for the 106 patients (68% female. 32% male, mean age 47.4 yers, range 15-82), The predominant site of fusion was lumbosacral 71.7%, and the predominant pathology degenerative 67.9%. Patient assessment of pain using a visual analog scale (VAS) of 0-10, revealed mean VAS scores at 3, 6 and 12 months of 1.64, 1.82 and 1.210. Pain at 12 months was less ( p < 0.01) when compared with pain at 3 and 6 months. Lumbar location of surgery and degenerative pathology correlated with increased pain scores ( p < 0.05). Some patients (10%) complained of sensory loss consistent with cluneal nerve disruption. There were no other neurovascular complications. The majority of patients have little residual pain from PIC bone graft donation, and initial symptoms tend to resolve to 12 months. There is increased residual pain associated with lumbar surgery, degenerative disease, and poor outcome. This suggests symptom origin may be unclear, and adjacent surgery may increase chronic pain perception when poor outcomes occur. The relationship among scar expansion, soft tissue defects at the site of gluteal reattachment, and local tenderness, suggests that connective tissue defects at the site of gluteal reattachment, and local tenderness, suggests that connective tissue healing properties may influence residual symptoms. This study suggests the risks of major complication secondary to PIC bone graft harvest are low, and it is very unlikely that a successful outcome from spinal surgery will be prejudiced by significant bone graft donor site pain.

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I 31 BRAIN RESEARCH CONFERENCE

Instrumentation of the Thoracic and Lumbar Spine with Lateral Mass Plates and Cables

F. M. FICHTEL" and H. MORGANb

"Depurtnient of' Neurological Surgery, Universit~~ of Tesas Southernwestern Metlicd Center at Dallas, Teras. US. and Departinelit of Neurological Surgery,

.4irc~klrrnd Hospital. rliickland, New Z e a h i d ; hDeprrrtriieiit of' Neurological Sitrgrrj.. Uniiwsit.v of Texas Southernwestern

Medicul Center ut Dallas. Tesas. U S

Over the past two years. I ? patients were identified as being at either low or high risk for becoming unstable after a decompressive spinal procedure. A complex instrumentation plan was undesirable for high risk patients. The primary procedure was decompression for treatment of degenerative disease. trauma. and tumour. Lateral mass plates designed for the cervical spine nere used. Cables secured the plates to the spinous processes. The plate was cut to fit, then plsced at the spinolaminar junction. The cable was passed through plate and spinous process, aioiding the spinal canal. Fusion was possible before or after placement of the instrumentation, as the low profile of the construct allowed easy access to the lamina and facets. No neurological deficits related to this method have been noted. To date, no patient has demonstrated instability. clinically. or radiographically. No hardware failure has been noted. Patients with pre-operative pain thought to be due to micro-instdbi\ity have had reductions in their discomfort. It is often difficult to predict whether a patient will be unstable following a spinal procedure. Factors such as the patients co-morbid conditions. risk of neural tissue injury, blood loss. and cost. may discourage or prevent one from performing a complex stabilisation procedure. However. instrumenting a patient at the time of the decompression avoids a second anacsthesia. the increased risk of infection and the increased technical difficulty due to scarring. This method is simple to perform. adds little time to the case. carries low risk of injury to neural tissue. does not usually require extra dissection. creates minimal blood loss, and is relatively inexpensive. The construct acts as a tension band, and the forces are thought to be distributed across multiple cables and spinous processes via the plates. Testing on a spine model has not been carried out. therefore added strength is not quantitatively known. Despite short follow-up, ths preliminary restiltb show this to he a safe and efficacious addition to the spinal surgeon's arnianientarium.

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Angiopathy in Hypothermic Nerve Injury

M. POLLOCK and J. JIA

Neurology Unit, Departriient qf Medicine, Uniwrsitj) of Otago, Dunedin. Mew Zealand

Non-freezing, cold nerve injury is uncommon in civilian practice but may reach epidemic proportions in war zones. Studied since the time of Hippocrates its aetiology has remained elusive. We have sought to replicate experimentally a peripheral nerve cold temperature grad- ient. since this has been emphasised in clinical descriptions. Nerve blood flow measurements and morphological examination of cooled nerve strongly suggest that the pathological bais of non- freezing nerve injury is ischaemia. Our observations of the vasa nervorum show that cold- induced intravascular aggregation is followed by a “no-reflow” phenomenon which culminates in endothelial damage and delayed thrombotic occlusion.

Hypertension and Diabetes Mellitus as Risk Factors of Single and Multiple Lacunar Infarcts and Leucoaraiosis

I. MOEBS

Departnient qf Psychological Medicine, Otago Medical School, Dimedin. New Zealand

The present study examined whether or not single and multiple lacunar infarcts and leucoaraiosis were related to hypertension and diabetes mellitus. The subjects were 242 ischaemic stroke patients with complete clinical and neuroradiological investigations drawn from the Berlin Stroke Data Bank 1991 -92. Diabetes niellitus was positively associated with multiple lacunar infarcts and leucoaraiosis (odds ratio 4.2; 95% confidence interval 1.7 - 10.4) and single lacunar infarcts [odds ratio 3.3; 95% confidence interval 1.3-8.2). A significant association between diabetes mellitus and single lacunar infarcts has never been documented in the literature. The other findings were consistent with prior research that reported the frequent occurrence of hypertension and diabetes mellitus in patients with multiple lacumar infarcts and leucoaraiosis. The results suggested that the pathology of single lacunar infarcts might be similar to that of multiple lacunar infarcts and leucoaraiosis.

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Quantitative Electroencephalography in the Differentiation of Alzheimer’s Disease and Vascular Dementia

E. SEAL, C. VAN HINTUM, J . PIERSON and R. HELME

Ncit iorir i l .4g~Irig Rrvetiri~h Iristititte. Poplar Rd, Parkville, Vic 3052, Australia

The diagnosis of dementia can be diflicult. Accurate diagnosis has important prognostic and therapeutic implications. Nevertheless. conventional electroencephalography (EEG) has always played a secondary role in dementia investigation. More recently quantitative EEG (qEEG) has allowed more detailed and objective analysis of EEG data. hut there is still no clearly defined clinical role for qEEG. We have used relative power qEEG data during rest and active brain conditions (serial subtraction and smell detection tasks) to differentiate between demented and non-demented subjects. and between subjects with known causes of dementia. Electroence- phalograms were obtained from 15 subjects with Alzheimer’s disease (AD). 16 with vascular dementia (VaD). and 16 control subjects. Discriminant function analysis was used to diKerentiate groups according to task, electrode site. and frequency band width. Eightysix percent were correctly diagnosed as demented or non-demented from qEEG comparisons of resting states with eyes closed and eyes opened. All subjects with A D and VaD were correctly diagnosed by qEEG recorded during smell detection. Quantitative EEG during serial subtraction correctlS diagnosed 910.b of this group. These results have important implications for future qEEG research. and may be pertinent to the clinical assessment of dementia.

Bax Expression in Alzheimer’s Disease Post-Mortem Hippocampus

G. A. MACGIBBON“, P. A. LAWLOR”. M. DRAGUNOW”, R. L. M. FAULLb and P. HUGHES‘

“Depurtriieiit of Pharr?iucolog>,. The Utiiversitj* of Aucklarid, Priwte Bug, Aitcklurid, New Zealund;

hDcpr i rw t t t of ..lnutor?ij., The Eriiversiij* of’ A uckluncl. Priwte Bag, ‘4 iccklaritl, New Zralaiid;

c24ririru.c Geroritologj. Ceritre, C1iiversity of‘ Sotrtlzern Culijbrriia, Los Arigeles, Culiforriici. U S

Recent studies indicate that the proto-oncogene Bax and related proteins (e.g., Bcl-2) may play a role in determining whether cells will undergo apoptosis under conditions that promote cell death. Increased expression of Rax has been found to promote apoptosis, while over-expression of Bcl-2 can inhibit apoptosis. Recent reports of increased levels of Bcl-2 in neurons in Alzheimer’s disease ( A D ) prompted us to investigate the expression of Bax in AD, and compare this with Bax expression in hippocampi of neurologically normal controls and Huntington’s disease ( H D ) . I n A D post-mortem hippocampi we found a concentrated localisation of Bax in senile plaques. which correlated with the localisation of ,j-amyloid protein in adjacent sections from the same brains. j-amylod positive senile plaques are thought to contribute to the A D process. possibly via an apoptotic mechanisms. and this may occur via an increase in Bax in these areas. Bax was also strongly stained in tau-positive tangles in A D hippocampi, suggesting Bau may play a rolc in tangle Formation. In addition. we observed a loss of Bax expression in the dentate granule cells of A D hippocampi compared with moderate Bax expression in control and HD hippocampi. and this loss may be related to the survival of these neurons in AD.

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BRAIN RESEARCH CONFERENCE I35

The Human Blood-Brain Barrier in Seizures: Mosaic Distribution of Endothelial Glutl Glucose Transporter

E. M. CORNFORD, S. HYMAN, M. E. CORNFORD and A. V. DELGADO-ESCUETA

Veterans Adininistration West Los Angeles Medical Center; UCLA School of Medicine; and Harbor-UCLA Medical Center; Los Angeles, California, US

Immunogold electron microscopic analysis of brain resections from patients undergoing surgery for treatment of seizures was performed. Samples were prepared from: 1) the most actively spiking epileptogenic site, and 2) the least actively spiking region, as indicated by intraoperative EEG monitoring. A bimodal Glutl distribution was observed. Approximately one half of the capillary profiles examined displayed abundant Glut 1 immunoreactivity on both luminal and abluminal endothelial membranes. In the remainder of the profiles examined we observed fewer Glutl epitopes, yet erythrocyte membranes were highly Glut 1-immunoreactive, suggesting that an absence of endothelial Glutl reactivity was not attributable to method artifacts. Modulation of glucose transporter activity in the blood-brain barrier (BBB) is characterized by a either the relative paucity of Glutl (on some groups of cells), or other sub-populations of adjacent (and even contiguous) endothelial cells exhibiting abundant expression of Glut 1 transporter protein. We hypothesize that in patients with complex partial seizures, BBB Glutl glucose transporter activity may be altered in the epileptogenic focus (in the interictal state) through changes in these two sub-populations. In comparison to previous of hemangioblastoma and brain injury, endothelial Glutl density is apparently reduced in the seizure resections.

Vestibulotoxicity Caused by an Aminoglycoside Antibiotic: A Case and its Treatment

C. L. DARLINGTON“ and M. POLLOCKb

“Departnient of Psycholog.v, and the Neuroscience Research Centre, University of Otago, Dunedin, New Zealand;

bThe Neuroscience Research Centre, and Department of Medicine, Dunedin School of Medicine, University of Otago Medical School, Dunedin, New Zealand

Aminoglycoside antibiotics such as gentamicin are used to treat life-threatening bacterial infections; however, they often produce nephrotoxicity and ototoxicity which are reversible if recognised early. The ototoxicity produced by gentamicin is confined mainly to the vestibular hair cells (‘vestibulotoxicity’) and may develop even when the daily dose is maintained within what is accepted as ‘safe’ limits (i.e., 3 - 5 mg/kg/day, i.v). The only treatment for irreversible vestibulotoxicity is vestibular rehabilitation therapy. We report the case of a 60 year-old male patient who received gentamicin treatment (3.7 mg/kg/day, i.v for 33 days) for bacterial endocarditis. Despite normal renal function and treatment with a gentamicin dose within the range accepted as safe, he developed oscillopsia (i.e., apparent movement of the visual world) and gait ataxia three weeks after the commencement of treatment. Video recording and electro- oculographic testing revealed a serve impairment of the horizontal vestibulo-ocular reflect (VOR). Electronic balance platform measurements showed an equally severe impairment of the vestibulospinal reflexes. The patient was admitted to the Vestibular Rehabilitation Program, and following exposure to a graded series of eye and head movement exercises over a period of 2 months, developed saccadic eye movements which, to some extent, compensated for his deficient VOR. Although he remains ataxic. his postural control has also improved.

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I36 BRAIS RESEARCH CONFERENCE

Fos Protein Expression After Immature Hypoxic-Ischemic Brain Injury

D. E. OORSCHOT. M. J. MEXTED, F. RANG1 and E. SCARR

Deprtr?ietit 41 Amitot?iy and Strirctural Biology, and the Neuroscieiice Research Centre, CSiiwrsitj. of’ Otago, Dunedin, New Zedarid

Increased expression of the mRNA of the immediate early gene c-.fos has been reported after immature hypoxic-ischemic brain injury. However. no studies have examined the temporal expression of Fos protein, which is the functionally relevant product of c:fos gene expression. Increased of Fos protein has been linked to cell death. We therefore examined whether Fos protein is expressed by dying neurons after immature hypoxic-ischemic brain injury. A well characterised immature rat model of hypoxic-ischemic injury at postnatal day seven was used. Three hypoxic and three normoxic control pups were studied per time point (i.e.. 0,2, 12, 24,48, 72 h post-treatment). Expression of Fos within striatal and other neurons was detected immunocytochemically. Fos protein was expressed within dying striatal neurons after hypoxia. However. detection was only seen in hypoxic pups that had >80% of their striatal neurons dqing within their hypoxic-exposed hemisphere. This expression was evident 0- 12 h post- injury: a time course consistent with increased crfos mRNA expression 0- 3 h post injury. Dying neurons within the hippocampus. medial habenul and cerebral cortex also expressed Fos when h a t a l damage was severe. These results suggest that Fos protein is expressed by dying neurons ivithin severely damaged brain regions from 0 - 12 h after immature hypoxic-ischemic injury. Whether Fos protein expression is a cause or consequence of neuronal death remains to be elucidated.

Supported by the New Zealand Lottery Board.

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Crossmodal Links in Attention and Inhibition of Return Between Audition, Vision, and Touch

C. SPENCE”, M. NICHOLLSb and N. GILLESPIEb

a Psychology Deparcment, Cambridge University, England; bPsychology Department, Melbourne University, Australia

We investigated crossmodal spatial links in the control of exogenous orienting and inhibition of return (IOR) following the peripheral presentation of spatially-uninformative auditory, visual. or tactile cues. In the first two experiments. participants were required to make a speeded- discrimination response (continuous 1’s. pulsed) for tactile targets presented randomly to either hand. Targets were preceded at a variable stimulus onset asynchrony (ISOms, 200ms, or 300ms) by either an auditory (Experiment 1) or visual (Experiment 2) cue presented to the same or opposite side as the target. Participants responded more rapidly and accurately when the cue and target occurred on the same side. In Experiment 3, tactile cues were presented prior to randomly intermingled auditory and visual targets requiring an elevation discrimination response (up Y S . down). Response latencies were significantly faster for targets in both modalities when presented ipsilateral to the cue. These results provide evidence that the peripheral presentation of spatially-uninformative auditory or visual cues results in the crossmodal exogenous orienting of tactile attention. and tactile cues result in the covert cross- modal orienting of both auditory and visual attention. Experiment 4 demonstrated that at longer stimulus onset asynchrony interval (950- 2250 ms) these R T benefits reverse to become a cost for responding to stimuli presented on the cued side. These results provide the first unambiguous evidence for crossmodal links in IOR between all combinations of auditory visual, and tactile stimuli.

Attentional Biases Play No Role in Perceptual Asymmetries

M. E. R. NICHOLLS

Department of Psychology, University of Melbourne, Parkville, Victoria 3052, Australia

Right ear (RE) and right visual field (RVF) advantages are known to exist for the recognition of verbal material. These right-sided advantages can be explained by structural or attentional mechanisms. Structural mechanisms focus on biases in the neural access the ears and visual fields have to the contralateral and ipsilateral cerebral hemispheres. Attentional mechanisms focus on biases in hemispatial attention. The contribution of structural and attentional mechanisms was investigated within the visual and auditory domains in groups of dextral subjects. Lexical decision and word recognition tasks were used to generate right-sided advantages within the auditory and visual modalities (respectively). Both tasks were intermixed with trials which required discriminations between stimuli which were neutral in relation to cerebral function. A tone discrimination task was used within auditory modality and a brightness discrimination task was used with in the visual modality. Pretests demonstrated that both tasks produced no perceptual asymmetry. but could be affected by shifts in spatial attention. Responses were faster in the RE and RVF of the lexical decision and word recognition tasks. No asymmetry emerged for the tone or brightness discrimination tasks. If the right-sided advantage observed for verbal tasks was the result of an attentional bias, a RE or RVF advantage should have been eivdent for the neutral tasks. The independence of the two tasks supports a structural model of peiceptual asymmetry. A structural model that takes into account the dynamic functional organisation of the hemispheres is proposed.

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13x BRAIK RESEARCH C O N F E R E N C E

Interactions Between Selective Attention and Alertness Following Right Hemisphere Damage in Humans

J . B. MATTINGLEY". I. H. ROBERTSON' and J . DRIVER'

Attention ha3 at least t u o components. alertness and selection. Alertness is a state of generalised recidinebs to respond ivhich can he triggered externally by warning stimuli, or internally by \ oluntar) strategies. In contrast. selective attention operates to enhance the procesing of stimuli at specific spatial locations. while suppressing irrelevant stimulus inputs. Damage to the right hemisphere in humans commonly produces deficits in both alertness and selective attention. Here \ve show that spatial selectivity is modulated by brief, externally- induced changes in alertness in patients \vith right hemisphere lesions. Patients with right parietal damage performed a temporal order judgement (TOJ) task which estimated their thresholds for determining the relative onset times of two visual stimuli presented separately to the left and right of tixation. The right stimulus mas consistenly perceived as preceding the left u n l e s the later led. on aierage. by - 500 ms. indicating ii severe delay in the time-course of 1 istial awareness for contralesional visual events. This rightward bias in spatial selectivity was abolished hy presenting brief. non-lateralised auditory warning stimuli 300- 1100 ms prior to presentation of the visual targets in the TOJ task. These findings suggest that attentional belectivit) and alertness are interdependent neural mechanisms and that exogenous alerting cues ina) modify visual awiireness hy inducing transient shifts in the spatial focus of selective attention.

Schizophrenic Patients Exhibit a Cue-Dependent Right Hemi-Inattention

J . G. PHILLIPS", M. E. DOWNING", J . L. BRADSHAW", K . S. VADDADI' and C. PANTELIS'

Left hemisphere dysfunction and defective internal cueing have variously been proposed to play ii role in schizophrenia. We used a cued movement task to address patients' attention for rightwards or Icftwards actions. Fifteen schizophrenic patients and their matched controls, were either cued or tincued when using the right or left hand to move a pen to targets on their right or left side. Pen tip position was sampled at 200 Hz with a WACOM SD420 graphics tablet. Schizophrenic patients ivere slower in initiating rightwards movements without a cue. Kinematic analyses revealed reduced abductive adductive differences in the shape of patients' mo\ements trajectclrios. implying subtle differences in interhemispheric communication. Schi/ophrcnia to some extent resembles a form of cue-dependent right hemi-neglect.

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Connecting Speech And Print: A Matter of Timing

M. PETER

Department of Psychology, University of Queerisland, Brisbane, Queensland 4072, Australia

This research investigated cross-modal contact between visual and phonological processing during simultaneous presentation of visually and aurally presented linguistic material. A bimodal presentation paradigm was used in which print and speech were presented in close temporal proximity. In order to study the structural characteristics and directionality of the cross-modal interaciton, the influence of matching and non-matching stimuli in both modalities was explored. The temporal development of cross-modal activation was explored by varying the Stimulus-Onset Asynchrony (SOA) between the visual and auditory stimuli.. Experiments investigated simple grapheme-to-phoneme activation at a relatively early stage of processing by using a forced-choice identification task and syllables as items. Results confirmed earlier findings that there is cross-modal activation between the graphemic and phonological systems that is not directionally constrained. Importantly, the critical parameter for obtaining significant cross-modal priming was the relative timing between the prime and the target. Thet outcomes of the experiments suggest that a printed word’s phonology is a code activated at the very onset of perception of the printed word. The observed cross-modal effects are due to the interaction of the phonology generated from print and the phonology evoked from speech.

A Study of Brain Electrical Responses to Music Using Quantitative Electroencephalography

B. BARBERa, J. M. PIERSONb, S. P. McKENZIEb and R. D. HELMEb

“Nationril Ageing Research Institute, Parkville. Victoria, Australia, Facult)! of Music, University of Melbourne, Parkville, Victoria, Australia; bNational Ageing Research Institute, Parkville, Victoria, Australia

Electroencephalography (EEG) is a non-invasive method of recording brain electric1 activity as it manifests on the scalp. Such electrical activity is known to be representative of mental activity. Its measurement and analysis have proven effective in a range of diagnostic and clinical applications. Quantification of the EEG (QEEG) by spectral analysis has facilitated the extraction of a great amount of detail from the data and this factor, together with the advantage of excellent temporal resolution provided by the method, has encouraged its use in exploring normal cognitive processes. The study examines the neurological responses of musicians and non-musicians when listening to music. It examines QEEG differences between music stimulus conditions and a resting state, differences between musically trained subjects and non-musicians and differences in response to different styles of music. The EEG data were collected from a group of highly trained musicians and a group with no musical training. Results demonstrate individual subject variability, changes in response to the experimental conditions across all spectrally analysed frequency bandwidths, and limited differences in responses to the contrasted styles. The two subject groups were clearly differentiated when QEEG variables were used in a Discriminant Function Analysis. We have concluded that QEEG has the potential to elucidate neurological responses to music.

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I40 BRAIK RESEARCH CONFERENCE

The Prefrontal Cortex and the Evolution of Mind

P. J . SNOW and D. C. TRUSSELL

Recently. many authors have attempted to relate the concept of mind to neurobiological studies of the brain. Unfortunately. many of these attempts have confused mind with consciousness. This is surprising for we accept that consciousness is a fundamental property possessed by all animals that have a cerebr,il cortex. yet many people consider mind to be a property possessed only hy humans. In man. "higher functions" have for long been recognised as dependent upon the integrity of the prefrontal lobes. These "higher functions". involve an awareness of our emotions and moods and also of our abstractions of the outside world and our concepts of plans. including even our appreciation of time. In eastern religion and mythology the mind is recognised as the site of abstract thought. Achieving control over the mind is considcrcd to be important in the negation of such thoughts Lvhich are not generally relevant to the demands of our immediate social or physical environment. Maintaining a state of "no mind" is therefore considered as keeping at one's disposal the great conceptual power of the mind, so that it can be applied to the immediacy of real-life situations. Recent neurobiological studies suggest that such ;I function is subserved by the most recently evolved, dorsolateral parts of the prefrontal lobes ~

;I region \\ hich receives inl'ormation and where sensory abstractions and the internal milieu of our hody are both represented.

Thoughts of M A 0 and Dick: Are Amine Oxidases Friends or Foes?

B. CALLINGHAM

It is alightly more than 3 bears since Dick Laverty was in my laboratory refining our assay methods for aniine oxidase activities. What emerged from his work and from that of others was the realisation that not only were there tivo isoforins of nionoamine oxidase (MAO; EC 1.4.3.4) hut that. in many tissues, a further tissue bound enzyme could be found. namely semicarbazide- sensitive amine oxidase (SSAO: EC 1.4.3.6). differing in substrate and inhibitor selectivity and wbcellular distribution. At that time Me were concerned with the ability of amine oxidases. in peripheral and brain tissues. to deamiane amiens to terminate their action or to regulate their coiltent in tissues. More recently. the possibility that amine oxidase activity could lead to toxicity has attracted attention through the implication of toxic radicals, generated by MAO, in the progression of Parkinson's disease. In peripheral tissues. toxicity has also been seen, when SSAO deadminates allylamine to acrolein. in rats, causing necrotic lesions of the myocardium and arterial smooth muscle. The endogenous amine SubstrdteS. methylamine and aminoacetone, produce potentially toxic aldehydes and free radicals in SSAO containing cells, which include the smooth muscle of blood vessels its well as mesangial and synovial cells. Simultaneous production of aldehyde and peroxide greatly enhances cell damage. In diabetes mellitus. for example. circulating concentrations of aminoacetone are enhanced. making such toxicity a real posihilit!

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NMDA Receptors in the Vestibular Nucleus: Their Role in the Development of Vestibular Disorders

P. F. SMITH

Department of Pharmacology, School of Medical Sciences, University of Otago Medical School, and the Neuroscience Research Centre,

University of Otago, Dunedin, New Zealand

Unilateral deafferentation of the vestibular nerve (UVD) results in a complex pattern of eye movement and postural disorders, caused by the loss of normal vestibular nerve input to the ipsilateral vestibular nucleus (“ipsiVN’)). Although the behavioural effects of UVD are severe in both humans and other mammals, a compensation process (“vestibular compensation, VC”) gradually develops in which the resting activity in the ipsiVN regenerates. This process, which is entirely independent of any peripheral recovery, can be disrupted by the administration, directly into the ipsiVN, of antagonists for N-methyl-D-aspartate (NMDA) receptor, but only within a critical period following UVD. By contrast, intra-VN administration of an NMDA receptor/ channel antagonist prior to the UVD has the opposite effect, reducing the severity of the labyrinthine syndrome. In this paper I propose that the activation of NMDA receptors inthe ipsiVN. at the time of UVD, plays a critical role in the induction of the labyrinthine syndrome, and that the process of VC is associated with a gradual down-regulation of NMDA receptors with in the ipsiVN. VN NMDA receptors may mediate a form of heterosynaptic long-term depression in which VN neurons become less responsive to remaining excitatory CNS inputs, and the gradual dissipation of this long term depression may be responsible for VC.

Roles for G-Protein Coupled Receptors in the Induction and Persistence of Long Term Potentiation in the Hippocampus

W. C. ABRAHAM

Department of Psychology, and the Neuroscience Research Centre, University of Otago, Dunedin, New Zealand

Long-term potentiation (LTP) in the dentate gyrus and CAI regions of the hippocampus is typically described as being induced by interactions between the a-amino-3-hydroxy-5- methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) ionotropic subtypes of glutamate receptors. It has become increasingly clear, however, that activation of G-protein coupled receptors by both glutamate and extrinsic afferents such as catecholamines play a crucial role in the induction. and establishing the persistence. of LTP. Our data, obtained from both awake animals and hippocampal slices, suggest that dopamine Dl/DS receptor activation, but not @-nordrenergic receptor activation is necessary for normal LTP induction in area CA1. The converse is true in the dentate gyrus. Activation of metabotropic glutamate receptors can also facilitate the induction and persistence of LTP, even when activated for tens of minutes prior to the LTP-inducing tetanic stimulation. These data suggest that a critical conjunction is required betwen intrinsic afferent activity and neuromodulatory inputs in order for plasticity, and thus possibly learning, to occur. The necessary modulatory signals may differ between brain regions, and thereby contribute to regional differences in learning rules.

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GABA Receptors and Memory

G. A. R. JOHNSTON. M. CHEBE and T. HINTON

There are three major subtypes of receptors i n brain for the inhibitor neurotransmitter GABA. GABA(A) and GABA(C) receptors are ligand gated chloride channels, while GABA(B) receptors are Ci-protein linked receptors. Examples of each subtype have been cloned. All neurones in brain appear t o have GABA receptors. while a t least 30% of them release GABA as ;I transmitter. I t n.ould be very surprising if GABA receptors were not involved in memory! Antagonism of GABA(A) receptors by bicuculline improves memory, while enhancement of GABX(A) receptor function by benzodiazepine agonists impairs memory. Muscimol, a GABMA) agonist, and GABA(C) a partial agonist. impair memory. Some GABA(B) receptor antagonist5 appear to enhance memory. An agent that acts a s an antagonist of both GABA(B) and GABA(C) receptors shows promise as a memory enhancer in humans. GABA(C) receptors rcpresent a net\ target for memory enhmciiig drugs. There may be a subtle interplay between the three subtypes of GABA receptors in memory. perhaps as a result of presynaptic effects on cholinergic and glutamatergic bystein.;.

From Mice to Men: Animal Models of CNS Disorders

A. J. MORTON

I n Lpitc of recent ad\riiices in understanding the genetic basis of Huntington's disease (HD). there I S currently n o treatment for H D and the prognosis for affected patients is dismal. The lack ufa\ail;ible treatment goes hand in hand Lvith our lack of understanding of the mechanisms underlying the progressi\e neurodegeneration which causes HD. In recent years a theory has emerged sufgesting that H D is caused by an underlying deficit in energy metabolism which make.; striatal neurones vulnerable to potentiall!. neurotoxic substances. This suggestion arises from dudies using animal models for HD. particularly the chronic 3-nitropropionic acid (3-NP)- intoxication model for HD. 3-NP is a suicide inhibitor of succinate dehydrogenase which causes bilateral striatal lesions M hen administered chronically to mice and rats. Although its usefulness i s limited by the unpredictabilitb of lesion development. we have used the 3-NP model to examine the role of ncuromodulators in the development of striatal damage. Our data suggest that modulation of striatal activity, not only by glutamate but also by dopamine. may be critically important for the de\elopmcnt of 3-NP-induced striatal lesions. The development of the chronic 3-NP model for HD. and most recently the generation of a transgenic HD mouse puts us at a new threshold of HI1 research. Both models hold much promise for furthering our understanding 01' the pathology of HD. and their importance will be discussed.

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The c-Jun Transcription Factor: What does it do?

M. DRAGUNOW, R. A. XU, A-M WOODGATE, P. A. LAWLOR. G. A. MACGIBBON, M. WALTON, N. BUTTERWORTH

and M. DURING

Departments of Pharmacolog~~ and Molecular Medicine, Faculty of Medicine and Health Science, The University of Auckland, Auckland, New Zealand

The transcription factor, c-Jun, regulates neuronal gene expression by forming DNA binding complexes composed of homo- (Jun-Jun) or hetero (e.g., Jun-Fos) dimers. We have found that c-Jun is induced in hippocampal neurons undergoing apoptosis after hypoxia-ischemia, and in surviving medial septa1 neurons following axotomy. The phosphorylation state of c-Jun as well as the dimerizing partner. regulate its DNA-binding activity, and perhaps biological functions. Thus, c-Jun may have different functions depending upon its phosphorylation state as well as its dimerizing partner (cFos during apoptosis and c-Jun during axotomy). We investigated the induction and phosphorylation of c Jun after okadaic acid-induced apoptosis and NGF- induced process outgrowth in PCI 2 cells. Okadaic acid produced a dose- and time-dependent increase of c-Jun and c-Jun phosphorylation that was followed by apoptosis. In contrast, NGF (50 ng/ml) produced c-Jun induction and process outgrowth, but no increase in c-Jun phosphorylation. Transfection of PC12 cells with a plasmid containing a CMV promoter and c- jun cDNA transcription cassette did not lead to apoptosis, but produced process outgrowth and lead to enhanced survival of these cells. Thus, the function of c-Jun may be regulated by its state of phosphorylation as well as by its dimerizing partners.

Supported by the Health Research Council, Auckland Medical Research Foundation, New Zealand Neurological Foundation and New Zealand Lotteries.

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Bovine Adrenal Cell Cultures As Models for Alcohol Dependence

J. M. LITTLETON

Pharriiac~olog!~ Groitp, Kirigs College, Lotidoti ST1'3 6 L X , UK., arid THRI C~'iiiwrsitj, of Kmritck)., Lrsirigtori. I< Y 40546-0236. USA

Adrenal medullary cells are of neuronal phenotype and. when grown in culture, express many of the same transmitter receptors. ion channels and second messenger systems found in adult neurones. They also appeal- to respond to chronic exposure to drugs in a similar way, thus one major adaptive response to alcohol in the brain is an up-regulation of L-type voltage operated calcium channels (VOCCs) on neuronal membranes. and a similar effect is seen in adrenal cell cultures chronically exposed to alcohol in the culture medium. This change seems to be an adaptive response to inhibition of calcium entry by ethanol and is G-protein mediated. The second messenger system involved in increased expression of the VOCCs may include protein kinase C. Among the consequences of the massive up-regulation of VOCCs caused by ethanol in this cell type are hyperexcitabilitj during nithdrawal as shown by increases in "transmitter" release (bj K + depolarisation and by glutamate). immediate early gene expression and cucitotoxicity. The relevance of the changes in this model system to alterations which occur during alcohol withdrawal iu I,iw will he discussed.

Problems in the Drug Management of Parkinson's Disease

J. P. SIMCOCK

Parkinson's disease is unique in that it I S the onl) neurodegenerative disease in which neurotransmitter replacement is effective therapy. This is because the major loss of neurones is in a single system (the nigrostriatal pathxvay) a i th loss of a single neurotransmitter (dopamine) in the striatum. In man) patients with idiopathic Parkinson's disease. treatment with a dopamine precursor. L-dopa. results in maintained improvement in motor function for several years. Hotvever. after about 16 years. the therapeutic response fails with end-of-dose symptoms. "on-off 'I symptoms. and dyskinesias. The end-of-close symptoms will be discussed in relation to the well understood peripheral pharmacokinetics. In contrast, the known central pharmacodynamics do not adequately explain "on-off '' symptoms in dyskinesias in terms of dopamine receptor function. Dopamine acts mainly through the striatal Dz receptors but some 11, agonism is needed for D2 active drugs to be maximally effective. Possible alterations in receptor function mediating dopamine-induced dyskinesia will he discussed. The understanding of the different dopamine receptors. both with regard to anatomic distribution and pharmacologic action could provide the basis for new antiparkinsonian medication. Another therapeutic problem which may occur later in Parkinson's disease is hallucinations. sometimes associated with psychotic delusions. These symptoms are aggravated by L-dopa and dopamine agonists. and are related to changes in dopaminergic neurones outside the nigrostriatal pathna). The symptoms are similar to those of schizophrenia. in which there is also an .ibnormalit> of dopamine receptor function. I n parkinsonian patients. treatment is with the n o \ d antipsSchotic agents clozapine or risperidone.

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Documents

Abstracts of the Fifteenth International Australasian Winter Conference on Brain Research Queenstown, New Zealand, August—September 1997