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Neuroscience Letters 464 (2009) 173–178

Contents lists available at ScienceDirect

Neuroscience Letters

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oradrenergic modulation of neuronal responses to glutamate in theestibular complex

assimo Barresi, Maria Caldera, Claudia Grasso, Guido Li Volsi ∗, Flora Licata, Francesca Santangeloipartimento di Scienze Fisiologiche (University of Catania), Catania, Italy

r t i c l e i n f o

rticle history:eceived 16 May 2009eceived in revised form 24 July 2009ccepted 14 August 2009

a b s t r a c t

Increases in firing rate induced in secondary vestibular neurons by microiontophoretic application of glu-tamate were studied during long-lasting applications of noradrenaline (NA) and/or its antagonists andagonists. Sixty-nine percent of the tested neurons, scattered through all nuclei of the vestibular complex,modified their responsiveness to glutamate in the presence of NA. The effects were depressive in a major-

eywords:oradrenalineestibular nucleiiring rateicroiontophoresis

ity (40%) and enhancing in a minority (29%) of cases. NA application depressed responses to glutamatemore often than it increased them in lateral, medial and superior vestibular nuclei, while the reverse wastrue for the spinal nucleus. The mean intensities of NA-evoked effects were comparable in the variousnuclei. The enhancing effects of NA were antagonized by application of the alpha2 receptor antagonistyohimbine, and their depressive effects were enhanced by the beta receptor antagonist timolol. It is con-cluded that NA exerts a control on the processing of vestibular information and that this modulation is

echa

exerted by at least two m

he function of the vestibular nuclei (VN) is to control postu-al adjustments and eye movements related to head movement12,13,26,34]. A significant proportion of the afferent fiberso VN are glutamatergic, in fact glutamate (GLU) is the neu-otransmitter utilized by primary vestibular afferents [14,15].lutamatergic fibers also contribute a large part of the bilat-ral projection from the fastigial cerebellar nucleus [8] andorm part of the network of commissural interneurons [2].he high concentration of GLU [15], GLU receptors [6,33] andLU transporters [7] found in all the VN provides more evi-ence for the important role played by this neurotransmitter.hort-term neuronal responses to GLU in the VN are excitatory14].

The VN also receive a significant noradrenergic projection fromhe locus coeruleus [29]. The prevalent effect of noradrenaline (NA)n the neuronal firing rate of VN neurons is a weak and diffuseecrease, mediated by alpha2 noradrenergic receptors [17]. Beta-

nd alpha1 receptors mediate enhancements in the medial vestibu-ar nucleus (MVN) [25].

In other parts of the central nervous system, however, NA-nduced modification of the background firing rate is less important

∗ Corresponding author at: Dipartimento di Scienze Fisiologiche (Città Universi-aria), Viale Andrea Doria 6, I-95125 Catania, Italy.el.: +39 0347 6965025; fax: +39 095 7384217.

E-mail addresses: glivolsi@unict.it, guidolivolsi@gmail.com (G. Li Volsi).URL: http://www.guidolivolsi.it (G. Li Volsi).

304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.neulet.2009.08.035

nisms involving alpha2 and beta noradrenergic receptors.© 2009 Elsevier Ireland Ltd. All rights reserved.

than neuromodulation, regarded as the most significant function ofthe amine. An influence of noradrenaline on glutamatergic trans-mission, consisting in the modulation of post-synaptic potentialsand/or of glutamate release and uptake, has been found in vitro innumerous structures such as olfactory cortex [5], hippocampal for-mation and entorhinal cortex [27], amygdala [11], cerebellum [18]and in vivo in sensorimotor cortex [31], lateral reticular nucleus[20] and spinal cord [30].

In this paper we describe the action of NA on the excitatory neu-ronal responses to GLU in VN. Our aim was to establish whetherglutamatergic neurotransmission in these nuclei is dependent onNA levels. In fact, stress states in the short term and aging in thelong term strongly modify NA content and dynamics of noradren-ergic receptors in the central nervous system [10,28]. This impliesthat the functions of nervous structures whose neuronal activity ismodulated by NA can be modified by stress and impaired by aging,at least in the absence of compensatory mechanisms.

Experiments were performed on 19 Wistar rats deeply anes-thetized with urethane (1.5 g/kg). Acquisition and care of laboratoryanimals conformed to the NIH guidelines (National Institutes ofHealth Publication No. 85-23, revised 1985), to the European Com-munity Council Directive (86/609/EEC) and to relevant Italian law.The experimental protocol was approved by the Institutional Ani-

mal Care and Use Committee (IACUC), the ethical Committee of theUniversity of Catania.

A five-barrel glass microelectrode was positioned by a microma-nipulator at coordinates corresponding to the vestibular complex[24]. The final point of each penetration in this structure was

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74 M. Barresi et al. / Neuroscie

arked by iontophoretic application of Pontamine Blue (Sigma)jected by the recording electrode (cathodal current: 20 �A,–10 min).

The electrode tracks and recording sites were identified in coro-al sections of the brainstem (60 �m thick) stained with Neutraled.

The five barrels of the microelectrode were used to record singlenit neuronal activity extracellularly and to apply pharmacologicalgents by microiontophoresis.

The recording barrel was filled with a 4% solution of Pontaminelue (Sigma) in 3 M NaCl (resistance: 7–12 M�). Action potentials,ecorded from single VN neurons, were rated as unitary and usedor data only if they had a signal-to-noise ratio of at least 3:1 andemained unmodified in amplitude during the tests.

Three barrels of the microelectrode were used for iontophore-is. One barrel contained monosodium glutamate (GLU, Sigma,00 mM, pH 8) and the remaining pair contained two of the follow-

ng: noradrenaline hydrogen tartrate (NA, Sigma, 200 mM, pH 4.0),lonidine hydrochloride (Tocris, 50 mM, pH 5.0), L-isoproterenolydrochloride (iso, Sigma, 50 mM, pH 5.0), yohimbine hydrochlo-ide (YO, Sigma, 20 mM, pH 4.5–5.0), timolol maleate (TIM,ocris, 20 mM, pH 4.5–5.0). All drugs were dissolved inater.

The microiontophoresis system (Neurophore BH-2, Medical Sys-ems) balanced currents automatically through a barrel filled withM NaCl to neutralize any voltage shift due to the applied cur-

ents. To reduce drug leakage during electrode penetrations, all therugs were retained by currents of small intensity (2–10 nA) andppropriate polarity delivered to each of the ejection barrels.

GLU was applied with brief (30 s) negative current pulses (up

o 100 nA), while NA and its agonists and antagonists were appliedith longer lasting positive currents (up to 20 min, 2–20 nA).

Whenever a unit was isolated, three applications of GLU wereade followed by three (or more) applications performed during

ontinuous ejection of NA or an agonist. Then, GLU was pulsed for at

able 1ffects of NA applications on GLU-evoked responses.

Nucleus Decreases

M (%) Cfraction n

LVN(23) 58.65 ± 6.17 0.66 ± 0.09 9MVN(10) 62.10 ± 7.63 0.64 ± 0.07 4SVN(9) 42.88 ± 13.77 0.61 ± 0.2 5SpVN(6) 44.6 0.83 1All 100% (48) 58.49 ± 5.13 0.65 ± 0.06 19(40%)

he table shows the mean ± S.E.VN: lateral vestibular nucleus; MVN: medial vestibular nucleus; SVN: superior vestibula

Table 2Actions of NA antagonists on GLU-responses.

Yohimbine (YO), N = 17; Timolol (TIM), N = 12

Antagonist Increased by NA agonists

AntagonizedYO (8) 6TIM (3) 0

Decreased by NA agonists

AntagonizedYO (6) 2TIM (5) 4

Unmodified by NA agonists

DepressedYO (3) 2TIM (4) 0

The table reports number of neurons.

tters 464 (2009) 173–178

least 5 min to check for recovery. In most cases the sequence wasrepeated and an NA antagonist was ejected simultaneously withNA.

The sequence of inter-spike intervals of each recorded unit wasused to calculate the firing rate over 1 s bins for analysis and 5 s fordisplay. The mean value of the firing rate recorded over a sequenceof 180 values (3 min) in the absence of any drug application wasdefined as mean background activity.

A modification of the firing rate by at least 2 SD from the meanbackground activity for at least 20 s was defined as a response toa drug application. The parameters used to quantify a responsewere the magnitude (M) and the contrast (C). M was defined as thenumber of spikes recorded during the response minus the num-ber of spikes fired in a period with the same duration precedingdrug ejection. C was defined as the ratio between these two values(signal-to-noise ratio). For each cell the mean M and C of GLU-responses were determined during a series of at least three trialsperformed under each of the tested conditions (in the absence orpresence of an NA agonist and/or antagonist). In each cell, differ-ent sets of single trials recorded under different conditions (e.g.GLU-responses before and during application of a NA agonist) werecompared with a two-tailed Student’s t-test (Mann–Whitney U-testfor the normalized data).

To normalize the effects, the action of a drug on the GLU-responses in a cell was expressed as a percentage of the magnitudeM (M%) and the fraction of the contrast C (Cfrac), evoked by GLUapplied alone to the same cell. A Kruskal–Wallis test for non-parametric data was applied to compare sets of neurons (M% andCfrac) recorded in the various nuclei. A paired test (Wilcoxon ranktest) was used to analyze the effect of antagonists in neuronal pop-

ulations.

The unitary activities of 63 vestibular neurons were recordedduring iterated, short-lasting applications of GLU. All neuronsresponded with an increase in firing rate that in a majority (84%) ofunits lasted less than 15 s after the end of the application.

Increases No responsive

M (%) Cfraction n n

130.7 ± 3.24 1.33 ± 0.12 6 8143.3 ± 13.23 1.07 ± 0.03 3 3

147 1.21 1 3145.6 ± 10.6 1.88 ± 0.43 4 1138.8 ± 4.34 1.55 ± 0.16 14(29%) 15(21%)

r nucleus; SpVN: spinal vestibular nucleus.

Enhanced Unmodified0 22 1

Enhanced Unmodified3 10 1

Enhanced Unmodified0 10 4

M. Barresi et al. / Neuroscience Letters 464 (2009) 173–178 175

Fig. 1. Effects of long-lasting noradrenaline (NA) application on the excitatory responses evoked by glutamate (GLU) in the vestibular nuclei.(A) Mean modifications of the responses to GLU (parameters: variation of magnitude, M% and fraction of the contrast, Cfrac) during NA application in the whole pool of testedneurons. In both graphs the dotted horizontal line indicates the reference values. The columns indicate three groups of units showing a significant decrease of responses toGLU during NA (black), an enhancement (grey), no significant response (white).(B) Mean magnitude (M%) and contrast (Cfrac) of changes induced by NA in GLU-responses for each of the vestibular nuclei (LVN: lateral vestibular nucleus, MVN: medialvestibular nucleus, SVN: superior vestibular nucleus, SpVN: spinal vestibular nucleus). The number of units is indicated in parentheses. The number of unresponsive neuronsin each nucleus is indicated in Table 1.(C) The histograms illustrate the number of spikes fired by two neurons of LVN and SpVN respectively. Each column indicates the number of spikes fired in a period of 5 s. Thehorizontal bars above the histograms indicate the duration of ejection of the indicated drugs at the given current. The mean firing rates recorded in the absence of any drugapplication represent the background activity. The GLU-evoked excitations are indicated by an increase in the firing rate under the horizontal bars. During NA application,excitatory responses to GLU of one neuron were depressed and those of the other neuron were increased. Both effects were reversible.

176 M. Barresi et al. / Neuroscience Letters 464 (2009) 173–178

Fig. 2. Action of the alpha2 receptor antagonist yohimbine (YO) and the beta receptor antagonist timolol (TIM) on NA-induced decreases, increases or no modifications ofGLU-responses.(A) Mean values of magnitude modification in each pool (M%) in the presence of NA agonists (black columns) and of NA agonists and YO together (grey columns). YOantagonized NA-evoked increases, enhanced NA-evoked depressions of GLU-responses and reduced GLU-responses in neurons unresponsive to NA.(B) Mean values of magnitude modification in each pool (M%) in the presence of NA agonists (black columns) and of NA agonists and TIM together (grey columns). TIMantagonized NA-evoked decreases of GLU-responses.( o neus duraT s wasb of the

eLto(esnGtitC

C and D) Examples of the effects of YO and TIM application on GLU-responses of twpikes fired in a period of 5 s. The horizontal bars above the histograms indicate thehe rate meter histograms show that an NA-induced enhancement of GLU-responsey TIM. The effects were reversible and recovery to control levels followed the end

GLU-responses were studied during long-lasting (1–20 min)jections of NA in 48 units. Twenty-three neurons belonged toVN, 10 to MVN, 9 to SVN and 6 to SpVN. Sixty-nine percent ofhe tested units modified their responses to GLU in the presencef NA. GLU-evoked excitations were depressed in 40% of cases19/48) and enhanced in 29% of cases (14/48). In three neurons thenhancement reversed into a depression by increasing the inten-ity of the ejection current. The mean values of M% and Cfrac and theumber of significant decreases and increases induced by NA on

LU-responses in VN are reported in Table 1 and illustrated as his-

ograms in Fig. 1(A–B). NA evoked more depressions than increasesn three nuclei (LVN, MVN and SVN) and the reverse, more increaseshan depressions, in SpVN. However, the mean values of M% andfrac were not significantly different in the various nuclei.

rons belonging to LVN and SVN respectively. Each column indicates the number oftion of the ejection periods of the indicated drugs at the current given.antagonized by YO whereas an NA-evoked depression was effectively antagonizedNA application.

Cfrac followed the same trend as M% in LVN, whereas some dif-ferences were observed in the remaining nuclei where NA inducedthe modulation of background activity also when applied at lowdoses. In SpVN, due to attenuation of the background firing rateinduced by the amine the Cfrac value was higher than M% (Fig. 1B).So, NA-evoked increases of GLU-responses appeared enhanced andNA-evoked decreases reduced. An opposite effect was observed inMVN.

Examples of these reversible effects of NA on the excitatory

responses to GLU of two vestibular neurons are shown in Fig. 1C.

Yohimbine (YO), an antagonist of alpha2 noradrenergic recep-tors, was tested in 17 neurons during long-lasting applications ofeither NA (10 units) or clonidine (7 units). The pool of tested unitswas divided into three subsets (Table 2): neurons that significantly

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ncreased their GLU-responses during NA or clonidine application,eurons that significantly decreased them and neurons whose GLU-esponses were unaffected by NA agonists. A significant (p = 0.0102)ntagonizing action of YO on the increases of GLU-responses wasecorded in 6 out of 8 tested units. In addition, NA-induced depres-ions of GLU-responses were enhanced by YO application in threeut of six cases and finally, in 2 out of 3 units unresponsive toA agonists, GLU-responses were depressed. Fig. 2A illustrates

he trend to a generalized reduction of the responsiveness to GLUnduced by YO application.

In 2 SVN units, excluded from the histograms in Fig. 2A, a pecu-iar and opposite effect was recorded consisting of an antagonisticction of YO on the almost total block of GLU-responses evoked bylonidine.

Timolol (TIM), an antagonist of beta noradrenergic receptors,as tested in 12 neurons during long-lasting applications of eitherA (5 neurons) or isoproterenol (7 neurons). The application of theA agonists depressed GLU-responses in 5 cases, increased them

n 3 cases and was ineffective in the remaining 4 neurons. TIMntagonized NA-induced depressions of GLU-responses in 4 out of 5ested units (Table 2). TIM had no significant effect on the remainingeurons. These data are summarized by the histograms of Fig. 2B,omparing the mean values of M% during application of NA agonistnd NA agonist + TIM.

Examples of the antagonistic action of YO and TIM are shown inig. 2C and D.

These results demonstrate that NA exerts a specific modulationf GLU-responses in VN neurons and that its action is either depres-ive (more frequent in LVN, MVN and SVN) or enhancing (morerequent in SpVN). The effects evoked by NA on GLU-responsesre independent of those induced on the background firing. In fact,omparison of M% and Cfrac values demonstrates that, at the dosesf NA applied, GLU-responses of single neurons in the vestibularuclei were either decreased or increased. At the same time, theackground firing rate of these neurons was usually unmodified byA application in LVN, reduced in SVN and SpVN and enhanced inVN in some cases.The NA-evoked decreases and increases of GLU-responses were

ediated by noradrenergic beta and alpha2 receptors respectively,oth of which have been reported in vestibular nuclei [21,22].he most studied effect of alpha2 receptor activation by NA ago-ists is the inhibition of GLU release, exerted at a pre-synaptic

evel. This type of modulation, observed in vitro in spinal cordeurons [16], controls nociceptive transmission [23] as well as sym-athetic drive [19] but can also be found in the superior colliculus35], the hippocampus [3] and in the amygdala [11]. In contrast,lpha2-mediated increases of GLU-responses were described in theypothalamus [4] and in the bed nucleus of the stria terminalis [9],eta-mediated increases in the amygdala [11] and in Purkinje cellsf the cerebellar cortex [18]. All the reported data were recordedn vitro.

In VN, we recorded alpha2-mediated increases frequently andlpha2-mediated decreases only sporadically. Therefore, althoughe found that the depressive action on GLU-responses was mostlyediated by beta receptors, we cannot exclude the possibility that

n small areas of VN, alpha2 receptors were also involved in theepression of GLU-responses.

In olfactory cortex, a low concentration of NA facilitates gluta-atergic transmission and a high concentration depresses it [5].

his result is in agreement with our observation that in some unitsncreased GLU-responses were converted into depressions during

ong-lasting application of NA. A late activation of dopamine recep-ors [32] might also explain the biphasic behaviour shown by a fewnits during NA application, but usually our responses showed noodification when the ejection was prolonged in time, suggesting

o late recruitment of non-noradrenergic receptors.

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tters 464 (2009) 173–178 177

Our experimental set-up can give little information on the rel-ative contributions of various receptors involved and on their pre-or post-synaptic location. On the other hand, extra-synaptic mech-anisms cannot be totally excluded, given that in some units longlatencies and durations of noradrenergic effects were compatiblewith volume effects of NA.

On the whole, these results indicate that NA can exert two typesof influences on GLU-induced excitations of VN neurons. Theseopposite responses might represent two different populations ofunits (e.g. projection vs. commissural units). The observation thatapplication of muscimol or baclofen in locus coeruleus inducedan enhancement of vestibulospinal reflexes [1] is consistent withthe depressive effects of NA application that we observed in themajority of our neurons.

On the other hand, coexistence on the same neurons of receptorsinducing opposite effects cannot be excluded, taking into accountthat alpha2 receptor antagonists had a depressive action on GLU-responses regardless of the type of NA-evoked effect. In any case,changes in NA content and/or of noradrenergic receptor distribu-tion, induced in the short term by stress and in the long term byaging, could seriously modify and impair the function of secondaryvestibular neurons.

Acknowledgements

The authors are grateful to Professor David Tracey for criticallyreading the manuscript and for revision of the English text. Thisresearch was supported by a grant from the Università degli Studidi Catania (Italy).

References

[1] P. Andre, E. Horn, O. Pompeiano, Microinjections of GABAergic agents in thelocus coeruleus modify the gain of vestibulospinal reflexes in decerebrate cats,Arch. Ital. Biol. 133 (1995) 47–75.

[2] B.A. Bannatyne, S.A. Edgley, I. Hammar, E. Jankowska, D.J. Maxwell, Networks ofinhibitory and excitatory commissural interneurons mediating crossed reticu-lospinal actions, Eur. J. Neurosci. 18 (2003) 2273–2284.

[3] S. Boehm, Presynaptic alpha2-adrenoceptors control excitatory, but notinhibitory, transmission at rat hippocampal synapses, J. Physiol. 519 (Pt 2)(1999) 439–449.

[4] C. Boudaba, S. Di, J.G. Tasker, Presynaptic noradrenergic regulation of glutamateinputs to hypothalamic magnocellular neurones, J. Neuroendocrinol. 15 (2003)803–810.

[5] G.G. Collins, G.A. Probett, J. Anson, N.J. McLaughlin, Excitatory and inhibitoryeffects of noradrenaline on synaptic transmission in the rat olfactory cortexslice, Brain Res. 294 (1984) 211–223.

[6] C. de Waele, M. Abitbol, M. Chat, C. Menini, J. Mallet, P.P. Vidal, Distribution ofglutamatergic receptors and GAD mRNA-containing neurons in the vestibularnuclei of normal and hemilabyrinthectomized rats, Eur. J. Neurosci. 6 (1994)565–576.

[7] J. Deng, F.X. Zhang, Y.W. Pang, J.L. Li, Y.Q. Li, Vesicular glutamate transporter-immunoreactivities in the vestibular nuclear complex of rat, Neurosci. Bull. 22(2006) 204–208.

[8] M. Diagne, C. Delfini, P. Angaut, P. Buisseret, C. Buisseret-Delmas, Fasti-giovestibular projections in the rat: retrograde tracing coupled withgammaamino-butyric acid and glutamate immunohistochemistry, Neurosci.Lett. 308 (2001) 49–53.

[9] R.E. Egli, T.L. Kash, K. Choo, V. Savchenko, R.T. Matthews, R.D. Blakely, D.G.Winder, Norepinephrine modulates glutamatergic transmission in the bednucleus of the stria terminalis, Neuropsychopharmacology 30 (2005) 657–668.

10] M. Esler, J. Hastings, G. Lambert, D. Kaye, G. Jennings, D.R. Seals, The influenceof aging on the human sympathetic nervous system and brain norepinephrineturnover, Am. J. Physiol. Regul. Integr. Comp. Physiol. 282 (2002) R909–R916.

11] B. Ferry, P.J. Magistretti, E. Pralong, Noradrenaline modulates glutamate-mediated neurotransmission in the rat basolateral amygdala in vitro, Eur. J.Neurosci. 9 (1997) 1356–1364.

12] E.A. Keshner, H. Cohen, Current concepts of the vestibular system reviewed. 1.The role of the vestibulospinal system in postural control, Am. J. Occup. Ther.43 (1989) 320–330.

13] R.J. Leigh, T. Brandt, A reevaluation of the vestibulo-ocular reflex: new ideas ofits purpose, properties, neural substrate, and disorders, Neurology 43 (1993)1288–1295.

14] M.R. Lewis, K.D. Phelan, P. Shinnick-Gallagher, J.P. Gallagher, Primary affer-ent excitatory transmission recorded intracellularly in vitro from rat medialvestibular neurons, Synapse 3 (1989) 149–153.

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[

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78 M. Barresi et al. / Neuroscie

15] H. Li, T.G. Godfrey, D.A. Godfrey, A.M. Rubin, Quantitative changes of amino aciddistributions in the rat vestibular nuclear complex after unilateral vestibularganglionectomy, J. Neurochem. 66 (1996) 1550–1564.

16] X. Li, J.C. Eisenach, Alpha2a-adrenoceptor stimulation reduces capsaicin-induced glutamate release from spinal cord synaptosomes, J. Pharmacol. Exp.Ther. 299 (2001) 939–944.

17] F. Licata, G. Li Volsi, G. Maugeri, L. Ciranna, F. Santangelo, Effects of nora-drenaline on the firing rate of vestibular neurons, Neuroscience 53 (1993)149–158.

18] K.C. Marshall, W.H. Tsai, Noradrenaline induces short and long duration poten-tiation of glutamate excitations of cultured Purkinje neurons, Can. J. Physiol.Pharmacol. 66 (1988) 848–853.

19] T. Miyazaki, H. Kobayashi, T. Tosaka, Presynaptic inhibition by noradrenalineof the EPSC evoked in neonatal rat sympathetic preganglionic neurons, BrainRes. 790 (1998) 170–177.

20] A.Z. Murphy, M.M. Behbehani, Role of norepinephrine in the interactionbetween the lateral reticular nucleus and the nucleus raphe mag-nus: an electrophysiological and behavioral study, Pain 55 (1993) 183–193.

21] A.P. Nicholas, V. Pieribone, T. Hokfelt, Distributions of mRNAs for alpha-2 adren-ergic receptor subtypes in rat brain: an in situ hybridization study, J. Comp.Neurol. 328 (1993) 575–594.

22] A.P. Nicholas, V.A. Pieribone, T. Hokfelt, Cellular localization of messenger RNAfor beta-1 and beta-2 adrenergic receptors in rat brain: an in situ hybridization

study, Neuroscience 56 (1993) 1023–1039.

23] Y.Z. Pan, D.P. Li, H.L. Pan, Inhibition of glutamatergic synaptic input to spinallamina II(o) neurons by presynaptic alpha(2)-adrenergic receptors, J. Neuro-physiol. 87 (2002) 1938–1947.

24] G. Paxinos, C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press,1986, 234 pp.

[

[

tters 464 (2009) 173–178

25] M.V. Podda, A.R. Johnston, E. Tolu, M.B. Dutia, Modulation of rat medialvestibular nucleus neurone activity by vasopressin and noradrenaline in vitro,Neurosci. Lett. 298 (2001) 91–94.

26] O. Pompeiano, Vestibulospinal relations: vestibular influences on gammamotoneurons and primary afferents, Prog. Brain Res. 37 (1972) 197–232.

27] E. Pralong, P. Magistretti, R. Stoop, Cellular perspectives on the glutamate-monoamine interactions in limbic lobe structures and their relevance for somepsychiatric disorders, Prog. Neurobiol. 67 (2002) 173–202.

28] P.J. Scarpace, I.B. Abrass, Alpha- and beta-adrenergic receptor function in thebrain during senescence, Neurobiol. Aging 9 (1988) 53–58.

29] R.J. Schuerger, C.D. Balaban, Immunohistochemical demonstration of regionallyselective projections from locus coeruleus to the vestibular nuclei in rats, Exp.Brain Res. 92 (1993) 351–359.

30] P. Schwarz, N. Yee, S. Mir, J.H. Peever, Noradrenaline triggers muscle toneby amplifying glutamate-driven excitation of somatic motoneurons in anaes-thetized rats, J. Physiol. (2008).

31] V.M. Storozhuk, A.V. Sanzharovsky, V.V. Sachenko, Interaction of glutamatergicand adrenergic inputs of cortical neurons during conditioning, Neuroscience 76(1997) 877–890.

32] N. Vibert, M. Serafin, O. Crambes, P.P. Vidal, M. Muhlethaler, Dopaminergicagonists have both presynaptic and postsynaptic effects on the guinea-pig’smedial vestibular nucleus neurons, Eur. J. Neurosci. 7 (1995) 555–562.

33] P.P. Vidal, A. Babalian, C. de Waele, M. Serafin, N. Vibert, M. Muhlethaler,NMDA receptors of the vestibular nuclei neurones, Brain Res. Bull. 40 (1996)

347–352.

34] V.J. Wilson, Physiological pathways through the vestibular nuclei, Int. Rev.Neurobiol. 15 (1972) 27–81.

35] Y. Zhang, R.D. Mooney, R.W. Rhoades, Effects of norepinephrine on the activityof visual neurons in the superior colliculus of the hamster, Vis. Neurosci. 16(1999) 541–555.