Brain Research, 550 (1991) 291-297 © 1991 Elsevier Science Publishers B V 0006-8993/91/$03 50 ADONIS 000689939116637H

BRESl~37

291

Lesions of parvocellular subdivisions of the hypothalamic paraventricular nucleus alter open field behavior and acquisition of

sensory and spatial discrimination

James P. Herman*, Garth J. Thomas, Stanley J. W~egand and Don M. Gash Department of Neurobmlogy and Anatomy, Umverstty of Rochester, School of Medicine and Dentistry, Rochester, NY 14642 (U S A)

(Accepted 18 December 1990)

Key words Ibotemc acid, Paraventncular nucleus, Vasopressm, Arousal, Memory

Rats with ibotemc acid (IBO) lesions of the hypothalamlc paraventncular nucleus (PVN) were compared with operated control ammals over a battery of tests designed to assess memory- and arousal-related behavioral processes At the dose employed m these experiments, lbotenic acid selectively destroys parvoceilular elements of the PVN, leaving magnocellular subdwlsmns relatively intact, allowing for experimental dissection of the influence of parvocellular and magnocellular PVN neuronal populatmns on the behavioral parameters measured IBO-treated rats showed a greater incidence of reanng behavior and exhibited greater levels of total and central ambulation m an open field than control rats Acqmsmon of both the sensory and spatml reward contingencies were retarded in the IBO-leslon group, however, no differences were evident between IBO-treated and control groups in an approach-avoidance test, nor in the ablhty to perform the spatml and sensory discrimination tasks to a criterion level of accuracy Histological examination verified that bdateral IBO lesions destroyed parvoeellular elements of the PVN, whde spanng the majority of magnocellular neurons Results suggest that parvoceilular PVN lesions alter behavioral performance via interactions with physiological systems govermng arousal level

INTRODUCTION

The role of neurons producing the neuropept tde

ho rmone vasopressin (AVP) in learning and memory has

been the subject of considerable controversy 4 7,8 Whtle

it is general ly agreed that administration of AVP can

influence per formance of memory- indica t ing tasks,

whether endogenous A V P neurons mteract directly with

memory s torage or retr ieval processes and/or serve to

affect memory via modula t ion of general arousal level

has not yet been defini twely de te rmined

Endogenous AVP neurons of the hypothalamlc para-

ventr icular nucleus (PVN) have been tmphcated m

regula t ion of central cardmvascular tone 26 and of corti-

cotropln ( A C T H ) release 2'18 (via interact ions with corti-

cotropIn-re leas ing factor 9) These putat ive functions are

associated with init iat ion of neu roendocnne stress re-

sponses and sympathet ic nervous system actwat lon, both

of which are evident In si tuations where behavmral

radices of stress are apparen t m exper imenta l subjects

(see refs 10, 11) A connect ion between endogenous

AVP neurons , endocr ine /au tonomic functmn and behav-

lor is suggested by an apparen t decrease in fear-

associated behaviors in animals genetical ly unable to produce biologically active A V P 12A6'25 Fur ther , AVP

adminis t ra t ion studies have demons t ra t ed a distract re-

lat ionship be tween faclhtatory effects of A V P and ana-

logues on memory- indica t ing tasks and A V P effects on

the autonomic nervous system (for review, see refs 14,

17) These data suppor t the hypothesis that endogenous

AVP neurons may influence behavior via actions on

systems governing magmtude and dura tmn of adapt ive

autonomic responses to envi ronmenta l stimuli 6

In the present exper iments , the re la t ionship be tween

AVP neurons pr imari ly concerned with endocr ine/auto-

nomic function and behaviora l per formance was assessed

by selective ibo temc acid ( IBO) lesions of parvocel lular

subdivisions of the hypotha lamic pa raven tncu la r nucleus

This region supplies the bulk of vasopressinerglc output

to autonomic nervous system nuclei 2° and the hypotha-

lamo-pl tu i ta ry-adrenocor t ica l stress axis (via the hy-

pophysial por ta l vasculature) 23 IBO inject ion, whde

rel iably des t roying parvocel lu lar PVN neurons , spares

the vast major i ty of magnocel lu lar AVP neurons in the

* Present address Mental Health Research Institute, Umvers~ty of Michigan, 205 Washtenaw Place, Ann Arbor, MI 48109-0720, U S A Correspondence J P Herman, Mental Health Research Institute, Umverslty of Michigan, 205 Washtenaw Place, Ann Arbor, MI 48109-0720, U S A

292

a d j a c e n t p o s t e r i o r m agnoce l l u l a r P V N ~, t he r eby al low-

mg d issec t ion of the b e h a w o r a l ef fec ts o f b r a m s t e m - and

m e d m n e m m e n c e - p r o j e c t m g A V P n e u r o n s f rom A V P

cells c o n c e r n e d p r l m a r d y with fired and e lec t ro ly te

ba l ance In add i t i on , I B O les ions obv ia te d a m a g e to t ibe r

t rac ts r unn ing m p rox imi ty to the P V N whtch may be

invo lved m ca r rym g m m n e m o m c m f o r m a n o n (such as

the m a m m t l l o t h a l a m i c t racts 22) Les ion and con t ro l rats

o f the R H A + / + s t ra ta were s u b j e c t e d to a ba t t e ry of

behav io ra l tes ts d e s i g n e d to assess o p e n field b e h a w o r ,

d t s c r t m m a t t o n i e a r n m g , spat tal m e m o r y , and a p p r o a c h -

avo idance b e h a v i o r

MATERIALS AND METHODS

Sublects Subjects were normal female Roman high avoidance rats (RHA

+/+) , bred in the wvanum quarters at the University of Rochester RHA +/+ rats were utdmed in these studies to obviate problems associated with extraneous behavioral varmbihty and to allow meaningful comparison with previous experiments I2 Original breeding pairs were acquired from Dr Carl T Hansen, Vetennary Resources Branch, National Inshtutes of Health All animals were housed in hanging wire cages in a humidity- and temperature- controlled room Rats were mamtmned on a 12 12 h light dark cycle (lights on 6 00 AM), and had ad hbitum access to water at all times W~th the exception of protocols involving food deprivation, rat chow was available at all times as well

The use of female rats in the present experiments was mandated by the breeding dynamics of our small breeding colony No attempt was made to control or monitor estrous cycle, it was assumed that in individually housed animals, estrous cychclty would be distributed randomly among subjects, and if anything, would bins against statistical rehabd~ty of the data

Surgical procedures Twelve female rats received bdateral pressure injections of 1 0 gg

IBO into the region of the PVN under chloral hydrate anesthesia (0 6 ml/100 g b wt of a 7% solution) (utdlzang the stereotaxic atlas of Paxmos and Watson 19) The details of the mjectlon parameters and surgical protocol have been described prevsously I3 An addi- tional 6 female rats recewed control operations (control group), consisting of the entire surgical procedure with the exception of lbotemc acid injection Animals were allowed two weeks to recover from surgery before the commencement of behavioral testing

Behavioral paradigms Open field behavior Open field testing was conducted in a 91 ×

91 × 30 cm square box, painted gray, with the floor divided into 20 perimeter and 16 central squares of equal size (15 × 15 cm) by hnes painted on the floor The apparatus was dlummated by overhead fluorescent hghting Animals were removed from their cages and mdwtdually placed m the center of the open field Behawors were observed through a one-way mirror from an adjoining room The total number of squares crossed (defined as movement of all 4 feet across a line dividing two squares), number of central squares crossed, number of rears (defined as hftmg of forepaws off the floor of the apparatus), number of grooming bouts, and number of fecal boll were recorded over a 300 s peraod, at the end of which the trial was terminated and the rat returned to its home cage Ammals received one trial per day on each of 4 consecutive days, with all testing conducted m the afternoon

Mula-modal sensory discrimination In this and the succeeding procedures animals were maintained on restricted diets, consisting of 7 g wet mash per day Weights were maintained at 85% of ad hbitum weight by dally supplements where necessary Behavioral

testing was begun one week following the be.ginning of restn,~tcd food retake The testing apparatus was a trough T-maze consNmg of a start box, two goal boxes (GB) and a small t.holce area "Iht floor of the maze consisted ol smooth pressboard inserts o~erlymg brass grids, and the maze was dlumlnated by a 7 5 watt mcandestent bulb located directly above the choice area

Prior to examining acqmslnon ot sensory d~scnminat~on, rats were adapted to the maze with a series of one-door trials, each of which consisted of a rat being placed m the start box the start box door opened, and 2 s later one or the other goal box door opened (counterbalanced according to a semi-random schedule) and the rat allowed access to wet mash m the goal box Ammals recewed 6 adaptation trials per day (lntertnal interval ol 10 mln) on each ol 8 consecutive days, at which point all rats were running rapidl~ m the maze (latency to eat <-5 s)

Discrimination trials were begun the day tollowmg the final adaptation session On each trial a pressboard insert covered with a plastic grad material was placed in one of the goal boxes (determined according to an irregular, balanced schedule) The discriminative stimulus (insert) prowded numerous sensory cues, including tactile, visual and perhaps olfacto D mformanon Rats were placed m the start box, the start box door raised, and 2 s later both goal box doors raised simultaneously allowing access to the entire maze Animals entering the box containing the Insert received reward, consisting of 10-15 s access to wet mash animals entering the plain goal box were confined for 10-15 s without reward All rats recewed 12 trials per day with the floor insert (CS+)(intertrlal interval of 10 mln), counterbalanced between sides according to a Fellows schedule s, on each of 4 consecutive days

Spatial memory Spatial memory was examined In the same T-maze, utilizing a delayed non-match to sample (DNMS) para- digm Testing was begun the day following the last sensory &scrlmmatlon session This paradigm employed a paired-run procedure which has been described prewously Iz Briefly on each trml subjects received a one-door information run, consisting of allowing access to one arm of the apparatus, followed by a choice run where access to both goal boxes was allowed, the animal having to select and enter the box opposite that rewarded on the information run in order to receive reward On all runs rats were placed In the start box, the start box door opened, and 2 s later either one (information run) or both (choice run) goal box doors opened All reformation runs were rewarded by 10-15 s access to wet mash, as were correct choice runs On incorrect choice runs rats were confined to the goal box for 10-15 s without reward The Interval between reformation and chmce runs was approx 20 s, and the mtertrlal interval was 15 rain Animals were given 6 pa~red trmls per day, with the goal box presented on the information run of each trml determined by an irregular balanced schedule, on each of 10 consecutwe days Data were grouped m blocks ot 12 trials for analysis

Approach-avoidance Approach-avoidance was tested m the same maze, this time with the pressboard inserts removed (revealing a grid floor) In this protocol, rats were allowed access only to the right goal box throughout testing Subjects were trained to run for th~s goal box over a series of one-door adaptation trials, given 6 trials per day on each of 3 days Reward was 10-15 s access to wet mash Latency to eat m the goal box was recorded on all trials All animals, having extensive experience m the maze, were running consistently and rapidly In the maze by the third day of testing (latency to eat <5 s) On the 18th trial, all rats received a 2 5 mA scrambled shock which was delivered across the grid floor and metal food dish each time they contacted the food Subjects were confined to the goal box for 60 s and the number of shocks received recorded, after which they were replaced into their home cages Post-shock testing began 24 h later, when animals were placed m the apparatus and given a series of post-shock trials identical m all respects to pre-shock trials, with food available in the goal box Three post-shock trials were given on each of 6 consecutwe days, and latency to eat m the goal box recorded (to a maximum default latency of 60 s)

293

Data analysts Behavioral data were analyzed by Student's t-test or two-way ANOVA with repeated measures, where relevant

Post-hoc analysss was conducted where indicated using Newman- Keuls test, if F-values were stgmficant

: ;,-< ~..< ?:..~t, gp

Fig 1 Representatmve sections through the paraventncular nucleus (PVN) of sham-operated (A, C, E) and IBO-lnjected (B, D, F) rats Panels A, B, C, D Cresyl violet stain Panels E and F lmmunohlstochemlcal stain for argmme vasopressm A control rat Parvocellular and magnoceUular subdwlsions of the PVN are prominent at this level of the nucleus B IBO-treated rat Section taken at the same rostrocaudal level as A Extensive neuronal loss is evident m parvocellular regions of the PVN (asterisks), with accompanying ghosis In contrast, wable magnoceilular neurons can be wsuahzed in the postenor magnocellular PVN A limited tissue necrosis Is present bilaterally m the ventral thalamus of th~s animal (arrows) Cell death also occurs in the anterior hypothalamus at this level Cell death is accompanied by extensive dilation of the third ventricle secondary to tissue loss C higher magmfication view of left PVN depicted m A Note the presence of parvocellular neurons m the medial parvocellular zone (outlined by arrows) The posterior magnocellular subnucleus is prominent at this level (large, densely stained neurons) D higher magmficatlon of left PVN depicted m B Cell death is evident m all parvocellular subnucle, at this level, the medial parvocellular region (between arrows) is shrunken and neurons-poor when compared with C Magnocellular neurons can be observed amidst the zone of heavy cell loss, indicating the ablhty of these neurons to survwe IBO treatment E posterior magnocellular dwmon of the PVN, sham rat, stained for AVP Note the presence of densely packed AVP-posmve neurons m th~s regmn of the nucleus F posterior magnocellular dwmon of PVN, IBO-treated rat, stained for AVP Many AVP-lmmunoreacttve magnocellular neurons survive inJection of lbotenlc acid, indicating resistance of this particular cell type to toxic effects of this neurotoxm I I I = third ventricle

294

Htstologr Following the end of behavioral testing all rats were deeply

anesthetized w~th Chloropent (Fort Dodge)(0 3 ml/100 g b wt ) and perfused w~th -200 ml Zambom's fixatwe Brains were removed post-fixed m Zambom's fixatwe overmght, and transferred to a 30% sucrose-Zambom's solut,on, where they remained untd they sank Frozen 25 ktm sections were cut in the coronal plane through the level of the PVN on a shdmg mJcrotomc, and alternate series processed for stalmng of N~ssl substance using Cresyl v~olet or ~mmunoh~stochem~cal staining for AVP-~mmunoreacUv~tv Immu- noh,stochemlstry was performed using standard ABC-P procedures (Vecta Stare k~t, Vector Labs ) Ant,serum to argmlne AVP was acquired from Miles Laboratories, and used at a ddut~on of 1 4000 (pre-absorbed with synthet,c oxytocm to ohvmte cross-reactw,ty) T~ssue from sham and IBO-treated rats were processed concomi- tantly

RESULTS

Anatomy A representatwe bilateral PVN lesion is dlustrated m

F~g 1 Criteria for a successful lesion were bdateral

ehmmatton of the vast majority of identifiable parvocel-

lular PVN neurons m the medial and lateral subdwlslons, w~th sparing of slgmficant numbers of magnocellular

neurons, as determined from Nlssl- and lmmunostamed

sec t ions (Fig 1A-F) A total of 8 IBO-treated rats

satisfied these criteria The remaining rats had e~ther

partml les~ons, undateral les~ons or m~slocated les~ons and were not included in the subsequent analysis

Magnocellular subdwls~ons of the PVN sustained d~stmct

but hmlted damage following IBO tnject~on which was by

and large confined to circumscribed regions at the to~.u~

of the mleCtlOn (area of the mlcroDpette tip) m Nlssl- stained sections In no case was cell loss m the magno-

cellular divisions of the PVN sufficient to suggest marked toxicity to magnocellular neurons Staining for AVP m

the mjectlon site (Fig 1E-F) revealed a hmlted los~ ot

magnocellular AVP neurons in IBO-treated rats All

complete PVN lesions were accompamed by hmtted

damage to the ventral thalamlc region (nucleus reumens)

and/or anterior hypothalamus, in some ammals, areas ot

local necrosis could be observed in ventral thalamus (e g

F~g 1B) The extent and pattern of damage outside of the

PVN was not consistent across ammals

Behavtor Bilateral PVN lesions had no demonstrable effect on

drinking behavior or body weight maintenance No

diabetes lnslDdus was evident m the leston group (not

surpnsmg, given the lntegrtty of supraoptlc nucleus AVP

neurons), and IBO-treated ammals showed no stgnificant

differences from controls in body weight (pre-operatwe tbotentc acid-treated rats, 214 8 _+ 7 0, controls, 214 0 +

8 8, terminal lbotemc acid-treated rats, 211 6 + 12 0,

controls, 220 7 + 22 2)

Open field data for the IBO-leslon and control groups

are summarized m Fig 2 A - D TyDcally, all rats spent the majority of any trml near the corners of the open

field, with actw~ty cons~stmg of brief forays along the

walls of the box, with occasional excursions into the

A 180

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Fig 2 Open field behavtor, ibotemc acid lesion (IBO) and sham-operated control (CON) rats A total squares crossed, B rears, C fecal 19011, D central squares crossed IBO lesion rats exhibited increased incidence of both total ambulation and ambulation about the center of the open field, and m reanng behavtor, as referred from slgmficant effects of group on each of these measures by two-way ANOVA (P < 0 05)

central squares Over the 4 days of testmg IBO-treated

rats exhibited significantly elevated levels of total ambu-

latton (F1,13 = 4 83, P < 0 05) (Fig 2A) and reanng (F1 ~3 = 6 70, P < 0 025) (Fig 2B) relatwe to control rats Ambulation m the central regaon of the open field was

also increased m the IBO-leslon group (Fl,~3 = 4 50, P < 0 05) (Fig 2D) No significant group by tnal mteracUons

were evtdent on the above measures Groups d~d not d~ffer

s~gmficantly m open field defecation (F~g 2C)

Both the IBO-leslon and control groups were able to

perform both the delayed non-match to sample (DNMS)

(Ftg 3A) and sensory d~scnmmatton (F~g 3B) tasks to

criterion accuracy (defined as 10 correct responses out of

any 12 consecutwe trials) However, IBO-treated rats performed the DNMS task rehably poorer than control

rats over the course of testing ( F I j 3 = 4 58, P < 0 05) Slgmficant group differences on blocks 3 and 4 (P < 0 05,

Newman-Keul s test) (Ftg 3A) lndscate a slower acqm-

smon of the spatml contingency by the IBO group

Retarded acqu~smon of the DNMS contingency was

15 m.. o o E o 0~

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A. Delayed Non-Match to Sample

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6O

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1 2 3 4 5 Session [ - - ; - CON'BO I

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Fig 3 A delayed non-match to sample (DNMS) task, B sensory discrimination task IBO-treated rats showed impaired performance of the DNMS task (significant effect of group on accuracy by two-way A N O V A (P < 0 05)), h tghhghted by stgmficant group differences on sessions 3 and 4 by post-hoe analysts (Newman-Keuls test) All ammais were performing the DNMS task at above-chance levels by session 5 [BO-leslon rats also showed a trend toward poorer performance on the sensory dlscnmmatton task (effect of group on accuracy P < 0 07 by two-way ANOVA) All ammals were performing the sensory discrimination at above-chance levels by session 4

295

A

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Fig 4 Approach-avoidance behavaor A latency to enter the goal box, last pre-shock and first post-shock trial, B goal-approach speed, reported as 1/latency x 100 A both the IBO and CON groups showed 24-h retentzon of shock, as determmed from stgmficant differences between pre- and post-shock goal box entry latency (P < 0 05, t-test) Groups dtd not differ m pre- or post-shock entry latency B groups dtd not differ m pre-shock (PRE) or post-shock running speeds, thus showmg stmdar rates of extmctton of the avoidance response

accompanied by altered choice behavior m the IBO-

lesion group Three of 8 IBO-trea ted rats exhibited

formation of posmon habits m the T-maze (defined as 12

consecutwe choices to the same goal box, regardless of

the goal box presented on the mformaUon run), whereas no control ammals were observed to do so (It should be

noted that the extent of PVN damage or damage to

thalamlc or hypothalamlc structures around the reJection site did not differ in any conssstent manner between

IBO-treated rats exhlbttmg posmon habits and those not doing so ) The IBO group also showed a trend toward

delayed acqulsmon of the sensory dlscrlmmatton task, as manifested in an effect of group on performance accuracy

which narrowly missed statistical rellabthty (F1A 3 = 4 04, P < 0 07)

Approach-avmdance data are summarized m Fig 4

Both groups showed a significant avoidance response on

the first post-shock trial, as measured by stgmficant increases m response latency (P < 0 05, t-test) (Fzg 4A) However , groups did not differ m avotdance latency on the first post-shock trml (Fig 4A), and showed slmdar rates of extmct~on of the learned fear response, as assessed by increases m runnmg speed over the 6 post-shock days (Fig 4B)

290

DISCUSSION

Previous les~on 2 18 and tract-tracing 2°21 2:~24 studies

clearly indicate that the parvocellular PVN provides an

important neuropeptlderglc mnervatlon of brainstem

cardiovascular structures and the external lamina of the

median eminence All animals included m our les~on

group sustained marked neuronal loss in parvocellular

subdivisions of the PVN believed to contribute vasopres-

slnerglc projections to these essential autonomic and

neuroendocrme structures Loss of magnoceilular neu-

rons providing vasopressinerglc (and oxytoclnerglc) input

to the neurohypophysls was limited The histological

analysis therefore suggests that the behavioral sequelae

of IBO lesions to the PVN are primarily the result of

parvocellular PVN damage, including AVP neurons

known to directly innervate neuroendocrlne and auto-

nomic systems The patterns of behavior observed in rats with IBO

lesions of the PVN are suggestive of an alteration in

emotionahty and/or arousal level Lesions of the parvo-

cellular PVN resulted in heightened incidence of central

and peripheral ambulation and Increased rearing in the

open field, trends which have been negatively correlated

with behavioral and physiological indices of 'fear' in rats I zs The differences observed between IBO-lesion

and control rats on open field behavior suggest that

lesions of the PVN attenuated cautious behaviors, such as

freezing and moving about the walls of the open field

The presence of exploration-oriented behaviors, such as

central ambulation and rearing, in the IBO group suggest that the open field data reflect behavioral changes which

cannot be easily explained by a general increase in

locomotor activity These results support the hypothesis that parvocellular neurons of the PVN are revolved m

regulating processes associated with initiation or main- tenance of behavioral responses to novel and/or fear-

evoking situations The treatise that the PVN may be involved m general

memory consohdatlon processes is not strongly supported

by the present data IBO-leslon did not affect retention

of shock avoidance, extinction of the learned avoidance

response or achievement of criterion performance of the sensory discrimination and DNMS tasks However, per- formance of both the DNMS and sensory discrimination tasks were impaired as a result of IBO lesion, suggesting an Impairment in ablhty to learn the discriminative cues required for accurate choice behavior under the respec- tive conditions

Comparison of the results of these experiments, involving destruction of the parvocellular PVN, with those of our previous study utihzlng VP-deflcient RHA dffdi rats (congemc with the RHA +/+ strain

employed m these studies) suggests that parvocellular AVP neurons play an important role m mediating the

behavioral changes observed m both situations RHA dJJ

dl ammals exhibit (1) increased central and peripheral ambulation and increased rearing in an open field relative

to RHA normal controls, (2) impaired acqmsmon ot a

delayed non-match to sample task relative to controls

and (3) show memory of shock and extraction of

avoidance m an approach-avoidance paradigm ~2 These

results are strikingly similar to those obtained m the

present study using control and IBO-les~on rats derived

from the same RHA strain The common deficit m the

~botenic acid lesion and congenital vasopressin-defioent

models is a lack of AVP-produclng parvocellular neurons m PVN The similarity of changes m behavioral perfor-

mance seen m RHA dl/dt and IBO-treated rats suggests a common mechanism may be revolved, namely, alter-

atlons m autonomic/endocrine function pursuant to re-

moval of AVP from relevant clrcmts Interestingly,

vasopressin-~mmunoreactlve terminals in limb~c struc-

tures related to learning and memory, such as the lateral

septum, amygdala, and hlppocampus ~, are derived from

extrahypothalamic structures (such as the bed nucleus of the stria terminahs) and are intact m rats w~th PVN

les~ons Therefore, it appears appropriate to suggest that

changes m open field behawor, retarded acquisition of

the DNMS task and poor performance of sensory

discrimination may stem from alterations m autonomic/

endocrine AVP circuits, rather than AVP systems directly Innervating structures implicated m learning and mem-

ory

Parvocellular neurons of the PVN are clearly of

essential importance in neuronaily mediated release of

ACTH and possibly m central regulation of blood pressure Previous lesion studies indicate that PVN ablation dampens stress-induced ACTH secretion 2 18 and

central pressor responses 26 In the present experiments,

IBO-lesion animals lacking parvocellular PVN neurons

display patterns of behavior generally consistent with a diminution of fearfulness in novel situations Consider-

atlon of the known physiological roles tot parvocellular PVN neurons and our behavioral data lead us to

hypothesize that ehmlnation of these neurons may effectively reduce, In parallel, the magmtude of ACTH and autonomic responses to environmental stlmuh The end result of such neurohormonal impairment may be translated into a reduction in fear-induced behaviors associated with unfamiliar properties of the environment, and perhaps a general decrease m the efficiency with which information is processed (via changes in 'arousal' level)

The results of these experiments support the hypoth- esis that endogenous parvocellular PVN neurons are

297

mvolved m physiological processes mediat ing endocrine,

autonomtc, and behavtoral responses to exogenous stim-

uli, serving to actwate the ammal and promote adapta-

tion to environmenta l change Destruct ion of the parvo-

cellular PVN, a major source of bramstem-projec tmg and

medmn eminence-project ing neurons, results m behav-

ioral changes conststent with reducttons m magmtude of

situation-specific fear responses, responses whtch are

associated w~th actwatlon of these stress systems The

behavtoral changes observed m IBO-t rea ted rats closely

resemble those observed m total AVP deficiency, further

suggestmg that parvocel lular AVP-con tammg neurons of

the PVN may play an tmportant role m endocnne /

autonomic processes underlying behavtor

Acknowledgements We gratefully acknowledge Victoria MacKay and Barbara Turney for invaluable teehmeal assistance, and Dr Kelth Truldlo for helpful comments concerning the manuscript Supported by MH08883 to J P H NS 19900 to S J W , andNS 15109 t o D M G

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