Brainstem correlates of gustatory similarity in the hamster

Brainstem Con'elates of Gustatory Similarity in the Hamster' DAVID V. SMITH,e JOSEPH

B. TRAVERS

AND RICHARD

L. VAN 13USKIRK

Departnlent o f I~.vychology, Utlil,ersit.i, ~/' ~Vvotning Laramic WY82071 ( R e c e i v e d 27 D e c e m b e r

1978)

SMITH. D. V., J B, TRAVERS AND g. L. VAN BUSKIRK. Bteilt~tem r ojgustatonv si~,tilt,,it)'in the httomte~ gRAIN RES. g ULL. 4(3} 359-372. 1979.--Responses of netn ons in the nucleus Ir~ctu s solil~rius (NTS) and palabrachfid pons (Pb pons) of the h;tmstel to 10 gustatory stimuli were comp;~red to beh~ViOl'al slm[iadfies among these compounds Animals were given ;i conditioned UlSIe aversion IO one of the l0 stimuB by pairing it with ;in induced g~slroimesfinal illness Followhlg lhi~ procedure. Ihe degree of ge neraliznfinn of the le~lrned tasle aVel'Si,m to each of the other compounds was measured, gehaviolal similardy profiles were derived for each slimulus from tile similarities in the generalization profiles of each pmr of compounds. The acloss neuron eorleklfions in the filing rates evoked by these stimuli ill the NTS cells corresponded quite we}} Io these behavioral profiles, as did these hound corlelafions among Pb pondne cells, exeep~ ful those correkuions invol~ing qnlnlne. Sncrose-besl cells in the Pb p(ms ~lre lop blo~ld]g responsive to account fol Ibe behavioral similarity functions for sWCcl-nlslillg stinlnll, zfihoug~ other besl-sgmulus clltegollcs of cells (NaCl- and HCIbest1 showed response profiles qtdte s~nlllar to (be be ha~ioral profiles. ~ls did ~lll hes~-sfimulus clnsses of cells in the N I ' S I'aste quality coding Conditioned tasle ~lversion NtlCiCiis Iractus solltadus Across neuron paucrns Gustatory sln~ilardy HanlstcI taste profiMs

SEVERAl. experimental approaches have been laken toward the b e h a v i o r a l c a l e g o r i z a t i o n o f g u s t m o r y stimuli. U s i n g a shock a v o i d a n c e procedure, Erickson I3] demonstrafed thal rats conditioned to avoid KCI w o u l d also avoid NbI,CI but not NaCI. A similar patlerrl o f stimulus genera l i z a t i o n was found with a n appetitive operant task [191. in w h i c h ruts w e r e trained to respond on o n e of t w o ~evers, d e p e n d i n g upon the taste o1" a p r e v i o u s l y conditioned stimulus. From t h e s e g e n e r a l i z a t i o n data. Morrison D g l c o n s l r u c t e d b e h a v i o r a l t a s t e profiles depicting the perceived similarity o f z n u m b e r of compounds to those r e p r e s e n t i n g the four classical taste qualities (i.e.. salty, sour. s w e e l , bitter). A n o t h e r l e c h n i q u e for d e t e r m i n i n g taste s i m i l a r i t i e s a m o n g compounds uses the t a s t e a v e r s i o n that occurs following association o f a g u s l a t o r y s t i m u l u s with gaSlrointestihal illness. F o r instance, rats poisoned w i t h LiCI will subs e q u e n t l y avoid NuC[ and avoid N H . C I and KC[ to a lesser degree 120]. T a p p e r anti H a l p e r n [371 also d e m o n s t r a t e d t h a t rats would g e n e r a l i z e from a conditioned taste aversion to Other stimuli with s i m i l a r tasles. Most recently, a conditioned taste aversion procedure w a s used by N o w l i s and F r a n k 124] to g e n e r a t e t a s t e quality profiles for the h a m s t e r similar 1o those constructed by Morrison f191 from operantc o n d i t i o n i n g data.

P:lrabr~lchi:l] ~OT~S

T h e dlformation derived fi'om t h e s e b e h a v i o r a l approaches Cml be compared ~o electropbysiologic~d responses recorded from neuzons in the g u s t a t o r y system. F o r e x a m pie, c o m p o t m d s that h a v e b e e n s h o w n hi the tat to h a v e similar tastes (3. 19, 201 e v o k e similm" patterns of activity across ~1 population o f g u s t a t o r y afferent ~bers [8/. On the basis of taste quality profiles g e n e r a t e d from conditioned lusle aversion data, N o w l i s a n d F r a n k 1241 suggesled that h a m s l e r s classify tasle along foul q u a l i t a t i v e d i m e n s i o n s that correspond to foul" n e u l o n types. T h e present study provides a compm'ison of gustatory responses of netu'ons in the h a m s t e r b r a i n s t e m Io tasle similarity profiles derived f r o m t h e g e n e r a l i z a t i o n s of hamsters f o l l o w i n g condilioned laste aversions, It has been s h o w n that l e f l e x i v e responses to taste stimuli a r e inlact in d e c e l e b r a t e ra~s [ I I ], and that therefore some d i s c r i m i n a t i v e m e c h a n i s m s capable of g e n e r a t i n g these behaviors e x i s t at this level of the nervous system. H o w e v e r , the sensitivities of taste-responsive n e u r o n s in Ihe b r a i n s t e m h a v e nol so f a r been a n a l y z e d relative to the p e r c e i v e d s i m i l a r i t i e s and differences a m o n g g u s t a t o r y stbnuli. Since Ihe h a m s t e r laste system is responsive Io a wide~ r a n g e of stimuli than that of /he ral, p a r l i c u l a r l y to s w e e t - t a s t i n g c o m p o u n d s [9], a comparison o f the electrophysiology of ~his species to its b e h a v i o r a l c a l e g o r l z a t i o n of g u s t a t o r y stimuli

'This research was suppor/ed in part by Nagonal Institute of Neu rologlca[ and Commumcative Disorders and Stroke Gnmt NS-1(1211 and Research Career De.'elopmcnt Award NS-O01~ to D.V.S. Thanks are due to Robert M. Theodore for asslstance in Ihe collection of Ihe beha~iomt dala, A portion of these resl}hs was presented at Ihe 197,qmeeting of the Society for Neurosclence. ~Requests for repgnls should he sent to Da,;d V Smith, Depaament of Psychology, Box 3415, Univers;ty Station. On~versity of Wyoming. L a ~ m i e WY 82071,

Copyright ~ 1979 ANKHO

I n t e r n a t i o n a l lnc.--0361-9230/79/030359-04501.90/0

3r,0

SMITH, TRAVERS AND VAN BLJSKIRK

should provide a f r a m e w o r k w i t h i n w h i c h to e x a m i n e the n a t u r e of g u s l a t o r y i n f o r m a t i o n processing. MV;'rltot~

o f 44 trials, l"hese stimuli w~re presented in four blocks of trials with t h e I 1 s l i m n l i r a n d o m i z e d w h h i n e a c h block. T h e h a m s l e r ' s response to e a c h stimulus was m e a s u r e d by the m e a n n u m b e r of licks d u r i n g t h e four 10-see p r e s e n t a l i o n s . Each 10-see trial w a s timed from the a n i m a l ' s first lick.

Ih,ha~ i,~rtd [gapeHmet~tx Anhmd~, T h h l y aduP m a l e Syrian golden h~xmsters (dle~or mtrattr w e r e used. r a n g i n g in w e i g h t f r o m 90 tel 129 g. E a c h anima] w a s e o n d i l i o n e d to avold o n e of ten c o m p o u n d s , f~rming tell ;iversion groups o f t h r e e h a m s t e r s each. T h e a n i m a l s w e r e housed i n d i v i d u a l l y a n d m a i n t a i n e d on ad lib 1~3od Ihroughout tbe e x p e r i m e n t , but o n l y given access to w a t e r during the t r a i n i n g and testing sessions. Apl~tlrtlllls nnd xlimldi T h e ~mimals w e r e trained a n d l e s l e d in ;I Plexiglas c h a m b e r , Ig.2 • 23.7,< 25 c m , w k h a floor of p~wallel brass bars. At o n e end of the c h a m b e r , c e n t e r e d 5.b e m a b o v e the grid Poor, w a s ;1 ro~llld opening. I cm in d i a m e t e r , ~hrough w h l c h the h a m s t e r could lick a stainless steel t h i n k i n g sp(~ll, Stimulns solulions w e r e presented from a 12 b o t 0 e r e v o l v i n g carousel thai posdiolled e a c h d r i n k i n g lube P.5 cm oulside the o p e n i n g in the c h a m b e r for a speclPed period of tlnle. This aiF.111gement allowed a c h a n g e in sbnudJ vgl free morose111 of the carousel and ~dso prevented inadvertent Iriggering of the d r i n k o m e t e r circuit used lo cotlnl the flumber of licks during the p r e s e n t a t i o n of a Minltthls SOhlriDn. ]n ol'der to prevent olthetory discrlmiaalion of the ~aste stimuli 1171.4 11d of the c o n d i t i o n i n g stimulus w a s placed in a small c o n l a b l e r positioned P.3 cm directly b e l o w the opcldng oll Ibe out side o f the c h a m b e r . T h e conditioning MilmdtlS (CP} w a s e i t h e r : 0.1 M sucrose. 0.1 M dlManiac. g.P3 M N a C b g.03 M NaNO:t. 0.(13 M N H I C I . 0.P5 M CeCIl, (I,P3 M MgSO~, 0,PP3 M H C L P.P03 M (;wt~ric acid, or g.0gt M q u i n i n e hydroehIorkle [QI.ICI). made in distiged w a t e r leotlduclivily ~ 4 . g x Ill r robes/pill). "these sobllions aud dislilled wilier w e r e al~o used as tesl sfimuli. All stimuli Wel'C premellled al room t e m p e r a t n r c (21"C). J'tt,cedm'e. I blmslers w e r e n~uh~tailled on a 23~/z-br w;ller d e p r i v a t i o n schedule durillg the IrainJng procedure. On the first day of tl:dning, l h e uninlld w a s phleed in tbc c h a m b e r a m l giVCll f l e e access IO disti)ted water, w i t h the d r i n k i n g t u h e inltiMly located jt~st inside the opening in the side of the chaalbey, T h e lube Wits Iben gr~thlally ~,ilbdrawn dttring the 30-alia session to ii dlslmlce of P.5 c111outslde the e h ; i m b e l . T h e anillnd WaS given 30 tl~hl access [o the ttlbe in this position on the second day and on the Ihird day w a s pblced on a n inlets'a} schednle, collsisfillg of 1O+sec #resentafions of distilled w a t e r a P e r n a l e d w i t h 2g-see inteltriul inte~,ats, for 50 u i a t s . Gustatory aversion was induced Oll the I~tlrth day, d~lriltg w h l e b 25 tri:ds e a c h of dislilled wllter and o n e CS w e r e presented on lids ~ntel'vld schedule. The. licking rule to these pl'esentadolls of tbe CS wits used as the~pl'ecolldJtlollillg control r a t e for e a c h Sthlltlhls, F i P e e n m i n m e s after the hlst trial. 1be anbll.d w a s g i v e n 11n thjecllon of cyeh~phospbtln~ide I 13(I ing[kg ] P), T h e Iiflh d a y w a s a r e c o v e r y perlod, dttlS~lg w h i c h l h e tlldllud remuilled in its h o m e cage on ad lib li~od and w b b o u t w a l e r , On tile sixth day. ~'hen Ihe a n i m a l w a s dTV:-hr w a t e r d e p r i v e d , the gcnetadizMio11 of the e o n d h i o l i e d taste aversion w a s tesled, Oi1 the f i l s l tr;al o f Ihe test session the Sthl~tdtls wa~ always dlstilled water, followed by the CS oli the ~eeond t r i a l T h i s procedtlre e n s u r e d Ihat the ~ninl[d w o u l d d l h l k w a t e r but a v o i d the CS before f u r t h e r testing wl~s condneted. T h e nnlmnl wlts then presented w i t h distilled w:~(cl" a n d e[ich of the lesl sfimtth fouF times e a c h for a total

Nettrophyvi~lo,vical Experbneo.'s I'/cpt/r~tliott ~l/It. t SOIItlitHI$. Action potentials w e r e recorded from 3P neurons in the nucleus lraeltlS solitarius (NTS) o f 18 a d u h h a m s t e r s , 16 m a l e s and 2 f e m a l e s , ranging in w e i g h t from 78 to 178 g. and from 3P n e u r o n s in the parabrachi;d regio~l o f the p e n s (Pb pons/ or 16 athdt m a l e h a m s t e r s , r a n g i n g i n weight from 87 ~o i31 g, E a c h a n i m a l w a s deeply a n e s t h e t i z e d by i n t r a p e r i t o n e a l injection o f e i l h e r sodium penlob~trbltal (60 mg/kg) or u r e t h a n r (1.7 gikg), "/'here w e r e no differences noted b e t w e e n these two agents in the response propelties of NTS neurons, although u r e t h a n e provkled a m u c h m o r e stable a n e s t h e t i c /eve/. AII the n e u r o n s in Pb p e n s w e r e recorded u n d e r sodium pentobarbi lab S u p p l e m e n t a r y injections w e r e given w h e n necessary In m a i n t a i n at d e e p level of anesthesia. T h e a n i m a l ' s body lemp e r a t u r e was m a i n t a i n e d at 37~ ( ~+ I~ and h e a r t rate was c o n t i n u o u s l y monitored. P r e p a r a t o r y surgery began with the i m p l a n t a t i o n of a tracheal c a n n u l a . T h e a n i m a l was then placed in a nont r a u m a t l e h e a d holder 14} a n d the bead angled nosed o w n w a r d 270 b e l o w h o r i z o n t a l w h i c h helped m i n i m i z e br;dnslenl m o v e m e n t s tx':suthng from breathing. An incision along the posterior m i d l i n e of Ihe skull was followed by parlitlon of the fascia and m u s c l e tissue and r e m o v a t o f the occipital bone and a m a j o r portion of the intelT, arie~al plate, F o r N T S recording, the posterior portion of the c e r e b e l l u m w a s aspirated In expose the dors~d surface of the b r a l n s l e m from the obex In the dorsal c o c h l e a r nucleus. I-he exposed b ~ d n s t e m was kepl moist wi~h Ringer solution. T h e c e r e b e F lure w a s left intact for recordings h-ore the Pb pens, Action potentials w e r e recorded extracellul[~rIy with e i t h e r gla~s-lnsulated t~lngsten microelectrodes, wi{b 2-7 tz exposed tip lenglh, or with 2 M NaCbPtted glass micropipe~es ( ~ 3 ~t llp d i a m e t e r ) The electrode was positioned o v e r ~he o b e x a n d flloeed a n t e r i o r l y and l a t e r a l l y to Ihe recording a r e a with a 3-way m i c r o m a n i p u l a t o r and d r i v e n vertically w i l h a Nurishlge h y d r a u l i c microdrlve. (The r e f e r e n c e to o b e x indicates the o b s e r v a b l e c o n v e r g e n c e of the caudal end of the IVth v e n t r i c l e on the dorsal surface of the m e d u l l a . T b i s does not correspond in Ihe rostral-eaudal d i m e n s i o n In the bislologically identifiable o p e n i n g of the central c a n a l into tbc l V t h v e m d c l e , w h i c h is approxirna(ely I.P m m rosm d to th~s o b s e r v a b i e l a n d m a r k . ) F o r N T S recording Ihe electrode w a s m o v e d 2.1 m m a n t e r i o r a n d 1.2 m m lateral to the obex. T a s l e - e v o k e d activity w a s typically recorded at this location, o r i m m e d i a t e l y a d j a c e n t In it, from 600 to 950/z b e l o w t h e surface of tbe b r a i n s t e m . This a r e a w a s hlstologir a l l y verified to be in the lateral a n t e r i o r portion of the NTS. T a s t e - d r i v e n a c t i v i t y w a s recorded from tap Pb p e a s a f t e r positioning the electrode a p p r o x i m a t e l y 4.3 m m a n t e r i o r a n d 1.35 m m Intend to the obex. from about 3.5 1o4.3 m m b e l o w the dorsal surface of the c e r e b e l l u m . B e c a u s e of the a n g l e of the head. the electrode passed caudal 1o the t r a n s v e r s e sinus, t h e r e b y avo[dlng e x c e s s i v e bleeding (e.g. 136]). N e u r a l acd e i t y was passed through a u11ity-galn high irnpedaller probe prior to a m p l i f i c a t l o n ' b y a Grass p511 preamplifier. Action potenthds w e r e m o n i t o r e d on a n o s c i g o s e o p e a n d a u d i o m o l t h o r , checked for spike a m p l i t u d e a n d w a v e r e r s

BRAINSTEM CORRELATES OF GUSTATORY SIMILARITY consistency on a storage oscilloscope and recorded on magnetic tape ( T E A C A-2340 or D a t a , Inc. 1400). T h e a n t e r i o r portion of the h a m s t e r ' s tongue was enclosed in a glass flow c h a m b e r fitted with a rubber m e m b r a n e so t h a t saliva w a s e x c l u d e d and l e a k a g e p r e v e n l e d . Solutions w e r e d e l i v e r e d through t h e tongue c h a m b e r from a system o f o v e r h e a d funnels v i a gravity flow at n r a t e of 8 ml/sec. T h e stimuli used to test the r e s p o n s i v e n e s s of e a c h n e u r o n w e r e the s a m e as those used in the b e h a v i o r a l e x p e r i m e n t , at the s a m e c o n c e n t m t l o n s , a n d w e r e p l e s e n t e d in a different rand o m o r d e r for e a c h n e u r o n , except that sucrose, N a C I , HCI and QHCI w e r e a l w a y s p r e s e n t e d before the o t h e r stimuli. T h e stimuli w e r e presented at r o o m t e m p e r a t u r e (21~ Proce~hoe. S t i m u l a t i o n with each c o m p o u n d lasted app r o x i m a l e l y 19 sec and w a s fol!owed by a distilled w a t e r rinse of at least 3g-see duration. T h e i n l e r v a l b e l w e e n stimulations was at least 2 rain in o r d e r to p r e v e n t t h e prolonged effects of a d a p t a t i o n 135,36]. At varic~us times during a stimulation sequence, s p o n l a n e o u s discharge r a t e w a s d e t e r m i n e d by flowing distilled w a t e r o v e r t h e tongue for ]0 sec. A f t e r recording from a taste-responsive n e u r o n the e l e c t r o d e penelratlon w a s c o n t i n u e d to at Least the ventral limit of tasted r i v e n activity, w h e r e a small electrolytic lesion ( 1 0 / x A l ~ r 10-15 seel w a s m a d e for subsequent histological reconstruction of l h e e l e c t r o d e p l a c e m e n t w i t h cresyl violet or Well stains. T h e location o f e v e r y cell recorded lu /he Pb puns w a s histologically reconstructed, but only a portion of those in the m o r e a n a t o m i c a l l y well-deflned NTS w e r e e x a m i n e d histologically. N e u r a l responses ~hat could be identified as arising from o n e ceg on Ihe basis o f u n i f o r m i t y of spike height and w;lveform w e r e photographed wifil n Grass k y m o g r a p h cameru at a speed sufficient to d e l i n e a t e single action potentials. 3 h e p l l l t l a l y neural response m e a s u r e from w h i c h o t h e r response characteristics w e r e derived w a s the n u m b e r of impulses occurring in the first 5 see of Ihe response. W h e n n slinluhls w a s r e p e a l e d for a p;lrficular neuron, t h e response m e a s u r e w a s the m e a n n u m b e r of imptdses/3 see. M a n y ileUfOllS in both N T S aTld Pb pOllS had a relatively high spontaneous rate w h i c h was o f l e n a significant portion of a celPs response to sfilntllation. To avoid c o n f o u n d i n g the response m e a s u r e , Ihe m e a n s p o n t a n e o u s rate for e a c h n e u r o n was r o u t i n e l y subtracted from its response ~o g u s t a t o r y stimulag u n . T h e r e f o r e , both e x c i t a t o r y and inhibitory responses m a y be seen in the neural data.

RESULTS

Gelleralion of 13elzttvioral Simi/cttity Coefficients A conditioned t a s t e aversion to a p a r t i c u l a r c o m p o u n d suppresses i n t a k e not o n l y of that s t i m u l u s but o f others as w e l l , primarily on 1be basis o f taste similarity [37,38}. T h u s , the m o r e similar t h e t a s t e o f t w o c o m p o u n d s t h e m o r e an a v e r s i o n to o n e should reduce t h e i n t a k e of t h e other. In g e n e r a l , l h e effects o f t h e conditioned a v e r s i o n s a m o n g t h e s e c o m p o u n d s w e r e reciprocal. T h a t is, t h e r e w e r e not a l a r g e n u m b e r of directional effects in w h i c h a v e r s i o n to o n e compound w o u l d suppress the i n t a k e of a n o t h e r but r~ot vice versa. Instances in w h i c h this did o c c u r w e r e r e l a t i v e l y inf r e q u e n t a n d t h e m a g n i t u d e s of the differences r e l a t i v e l y small. T h e r e f o r e , the effects o f the conditioned a v e r s i o n for e a c h p a i r of c o m p o u n d s w e r e averaged, e.g., the suppressed licking to d l - a l a n i n e following a n a v e r s i o n to sucrose w a s a v e r a g e d w i t h the suppressed licking to sucrose following an

aversion IO dl-alanine. Examination o f these mean suppression scores for any one compound in relation to the olher

n i n e sfimull wi}l s h o w the e x t e n t to w h i c h h a m s t e r s tend to g e n e r a l i z e f r o m the taste of o n e c o m p o u n d to t h e others. T h e s e relationships for sucrose, dl-alanine, and N a C I c a n be seen g r a p h i c a g y in Fig. IA. T h e m e a n difference in licks/]0 see b e l w e e n pre- a n d post-conditioning sessions for e~lch c o m p o u n d a r e s h o w n in relation to sucrose (top), dl-alanine (middle), and NaCI (boltom). Obviously, the licking r a t e to sucrose following a v e r s i o n (o sucrose is q u i t e suppressed (top o f Fig. IA), and the g e n e r a l i z a t i o n b e t w e e n sucfose and di-alnnlne (top and middle o f Fig. IA) is a l m o s l as greal, indicafing that t h e s e a n i m a l s are Ireating t h e s e t w o corn pounds as if t h e y w e r e q u i l e similar in taste. On t h e o t h e l blind, I h e r e is no effect of NaCI aversion on t h e licking r a t e to sucrose, or of s'lcrose a v e r s i o n on the i n t a k e of NaCI (top and bottom of Fig. IA). This implies that the animars z,re j u d g i n g sucrose and NaCI to be q u i l e different in taste. T h e sucrose function in Fig. IA, t h e n , represents t h e degree to w h i c h t h e s e a n i m a l s perceive sucrose to be similar in l~lste Io "these o t h e r compounds. L i k e w i s e , the dl-alanine and NaCI functions r e p r e s e n l the s t i m u l u s g e n e r a l i z a t i o n s a m o n g t h e s e t w o s t i m u l i a n d the others. It is c l e a r in c o m p a r i n g t h e s e profiles t h a t if t w o compounds a r e j u d g e d to t a s t e a l i k e (e.g., sucrose a n d dl-alanine) their srimutus genemLizafion profiles a r e q u i t e simfiar, w h e r e a s two compounds that do nol gene r a l i z e to o n e a n o t h e r (e.g., sucrose and NaC() s h o w q u i t e different patterns o f g e n e r a l i z a t i o n across the ten compounds. T h e dashed fines in Fig. IA s h o w the m e a n differonce in licking r a t e to distilled w a t e r b e t w e e n the pre- and p o s l - c o n d h i o n l n g sessions. T h e e n o r bars about e a c h point indicate § 1 s t n n d a i d e r r o r of the m e a n difference and provide an indication of the a m o u n t of variability ~ssociated with these measures. A n o t h e r w a y of quanrifying this type of b e h a v i o r a l d a l a is to express the a v e r s i o n as a p e r c e n t a g e of the prec o n d i t i o n i n g licking rate to each compound [24J. This procedure c o m p e n s a t e s tbr differences in ~be pro-conditioning licking r a t e to 1he varions s~imuli (e.g., N a C 1 - 3 8 . 0 licks/10 sec, H C I - 2 5 . 5 iicks/10 see). T h e p e r c e n t a v e r s i o n s to these s t i m u l i , i s g i v e n in Fig. IB as I.O - post-conditioning ]icks/pre-condltioning l i c k s T h e p e r c e n l aversion s h o w n h e r e h a v e b e e n further corrected for t h e slight reductions in the licking rates to distilled w a t e r on the post-conditioning day (dashed line, Fig. IA) by a d d i n g the post-conditioning/pro-conditioning rath) for distilled w a t e r to the ratio for each c o m p o u n d before s o b t r a c r n g from I.O. A l t h o u g h t h e percent aversion m e a s u r e s shown in Fig. IB provide a fairly good indication o f stimulus g e n e r a g z a t i o n , these functions a r e based o n l y o n / h e perceived simfiarity o f individual pairs or c o m p o u n d s T h a t is, t h e similarity 9 f Stlcruse and dl-alanine is derived from the generalization of each of ~bese c o m p o u n d s to the other. Additional i n f o r m a t i o n about t h e similarity a m o n g t h e s e c o m p o u n d s can b e derived f r o m the s h a p e o f l h e g e n e r a l i z a t i o n functions (Fig." IB), as noted above. F o r e x a m p l e , the percent a v e r s i o n functions for sucrose and d l - a l a n l n e across t h e ten stimuli (Fig. 1B) a r e q u i t e similar. T h e degree to w h i c h t w o c o m p o u n d s t a s t e a l i k e should be related to the similarity of t h e s e g e n e r a l i z a tion functions. T h u s , t w o compounds w i t h similar tastes should g e n e r a l i z e [o l h e o~her stimuli in a v e r y c o m p a r a b l e m a n n e r , i.e., t h e i r p e r c e n t a v e r s i o n functions w o u l d be highly c o r ~ l a t e d . T h e s e correlations w o q l d indicate nol only the degree to w h i c h two compounds taste like o n e a n o t h e r , but also h o w w e l l their s i m i l a r i t i e s to the o t h e r stimuli t o r t e -

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PIG. t Procedure for gene~ldng Ihe behaviocal slmiladty coefficlents among the I0 guslatory stinluli, A: Mean difference in ficklng ~ e to I0 stimuli in r'eladon to suelose (top). dl ahmine (middle). and NaCI (bo~tOnl). between pre- and post-condigoning sessions. The dashed lines shows Ihe mean difference in licking rule Io distilled water. Slandard errors or the mean difference ~lre shown aboul e~lC~point. B: Percent aversion to each pair of sgmug, corrected for reducllons in Ihe licking rate to distilled wlner seen between pre- and post-conditioning sessions. C: Behavioral simgadty c.erficlems, derived from the Pearson product-moment correlation between each of the percent averslon functions. The lhree figed symbols in each function are those de fired from correlatlo~s among ~he ~h~e aversion functions in g

spond. B e c a u s e this m e a s u r e provides a m o r e c o m p l e t e descdplion of t h e gustatory similarities a m o n g t h e s e stimuli, it is used as t h e descriptor of behavioral s i m i l a r i l y t h r o u g h o u t Ibis paper. Correlational profiles for sucrose, dl-alanine, a n d NaC[ a r e s h o w n in Fig. IC. T h e coefficient for e a c h stimulus w d h itself in Fig, tC is i~ssumed to b e + 1 . 0 . since e a c h perccnt a v e r s i o n function for a n y c o m p o u n d (Fig. IB. stzerase, for instance) would correlate p e r f e c d y with itself. The filled symbols in Fig. IC represent t h e correlatlon coefflcients (Pearson r) a m o n g the t h r e e a v e r s i o n functions in Fig. IC (i.e., s u c r o s e • s u c r o s e x NaCI a n d N a C l x d l ahmine). T h e r e m a i n i n g points in Fig. I C ( w i t h o u t symbols) w e r e derived by correlating the percent a v e r s i o n functions for sucrose, d l - a l a n i n e alld NaCI w i t h t h o s e for the o t h e r

c o m p o u n d s . A corrcladonal profile w a s similarly derived for e a c h c o m p o u n d , a n d t h e s e functions are presented l a t e r in c o m p a r i s o n to electrophysiological d a t a from n e u r o n s in t h e h a m s t e r brainstem (Figs. 5 and 6).

Nt'tlrol Respon,~esfrom the Hamster Broinsteat Responses w e r e recorded to e a c h o f the 1O stimuli f r o m 30 neuronsinthehamsterNTSand3OinthePbpons. Theareas of t h e b m i n s t e m from w h i c h t h e s e 60 cells w e r e isolated a r e depicted in the charts s h o w n in Fig. 2. T h e shaded a r e a s in the figure s h o w the location o f taste-responsive n e u r o n s in the m e d u l l a and pans, as verified through histological rec o n s t r u c t i o n of the recording sitesl A l t h o u g h the r e s p o n s i v e

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pons FIG. 2. Traced sections from the laste-responsive regions of Ihc hamster medulla and pens, showing (shnded) ihc nreils from which gUSlalory-responsive neurons were isolated, The distance of lhese sections from obex are indicated ~ext Io each chart, Abbrevlations: Be. brachlum conjuncgvum; DVn. descending Veslibular nucleus; Mes V, meseneephalic IdgemlnM nucleus; NTS. nucleus tmetus solgarius; nVm. trigeminal motor nucleus; nVll. facial motor nucleus; pV. principal sensory tdgeminal nucleus; pyr. pyramidal tract; sV. spinal Irlgeminal nuclei.

a r e a s m a y extend a few h u n d r e d microns in the rostral* caudal d i m e n s i o n , a section from the c e n t e r of this e x t e n t is s h o w n for e a c h level, its distance rostraI to obex b e i n g indicated on the figure. Photographic records o f t h e responses o f o n e o f t h e N T S n e u r o n s to the ten g u s t a t o r y stimuli and distilled w a t e r a r e s h o w n in Fig. 3. O f the stimuli that r e p r e s e n t the four classical taste qualltles (i.e., NaCI. HCI. sucrose a n d Q H C l l . t h i s

unit responds best Io NaCI (X = 106 dnptllses/5 see), then IO HCI (X=50 impnlses/5 sec), QHC1 (X= 16 impulses/5 sec) a n d leasl to sLicrose ( X = 5 impulses/5 see), T h e r e is a very b r i e f t r a n s i e n t suppression following sucrose s d m u l n d o n , whicb also occurs to stimulation wilb dl-alanlne. These hnpulse counls, as all those reported in this papeJ, have been adjnsled for m e a n s p o n t a n e o u s firing r a i n (to flowing disLilled Wnlel). O f t g e tell sliinuli, this unit respomls besl IO N a N O s ( 132 impulses/5 sec) al~d s h o w s ' e x c i l a t o r y responses 1o all the colnpounds except t bose jtidged (o be s w e e t by in;in (sucrose a n d dl-alanine). C o m p a r e d to the o t h e r cells in the NTS. this oetlron is Mighily m o r e broadly responsive thun average. T h e profiles o f the responses of e a c h of the 30 N T S cells a n d Ihe 30 u n i l s fi'onl the Pb pOllS IO Ig sllnlllll a r e shown in Fig. 4. Cells iii e a c h level h a v e b e e n g i ~ u p e d according to w h i c h of Ibe four basic slinudi (i.e., sucrose, NnCI, HCI o r QHCI) e v o k e d the greilteSl exeitntOly r e s p o n s e hi 5 sec, a n d ranked w i l l d n e a c h glOup for response n l n g n d u d e Io lids hesl stimuhls, T h e l e f o l e , cells ill the NaCl-besl grotlps respond b e t l e r Io NaCI than Io file o l h e r t h r e e basic stimnli (SllCl'OSe. HCI or QHCI), b m m a y icspolld sonlewhut b e t l c l 1o o n e or the o t h e r six stimuli Ihan to N a C L T h e cktssilqcatlon or neUlOl/S into o n e of Ihese four <'basie-slimuhls" c a t e g o l i e s follows tile suggesllon that t h e r e m a y be four dislinci neul"nl c h a n n e l s i n v o l v e d ill the coding of l a s l e q u a l i l y 124.291, and provides the n e c e s s a r y cutegul'izalion for tile COlllp;lliSOil of responses in t h e s e " c h a n n e l s ' " to the bchavior;d s i n l d a r h y coellqcients (see Figs. 7B and 8]]}. A l t h o u g h such a chlssiflcatlon depends ripen Ihe concelllr~llions of Ihe stintLlli, these stinluli Hl'e presented nl mid-range inlensilics, ~lnd ntos[ i m p o r t a n t l y , t h e c o n c e n t r a t i o n s of t h e stimuli arc Ihe s a m e ill holh Ihe neul'id 011d b e h a v i o l a l e x p e r i n l e n l s . The o~dinate for this 3-dimensional figule is Ihe iltlnlber of illlptdses/5 sec, ~ll(hotlgh it is not lahelled Oll tile figure, This Incasure (COl'reeled for 5pOIlliUleOiiS ralc) Hnges Ii'on1-9 IO 468 impulses/5 sec in N T S n e u r o n s and from 45 It) ,I50 impulses/5 sec ill p o n l i n e neurons. Allhoug]l this 3-dimenslonnl r e p r e s e n l a t l o n shows t i n n i l y Ihc bl~adlh of responslvenes~ of t h e s e ceils and Iheh" r e l a t i v e responsivehess within and b e l w e e n besl-stimulus c~llegolies, a pOllion of these responses Cill/npl be seen b e c a u s e of the o v e r l a p in t h e response profiles. T h e differences o f sinbbu'ities ill die paRerns of neural a c t l v b y evoked across e i t h e r of tbese cell populations by :lily pair o f s t l m i d l ciln be seen Ily reading tile ngule from front to back. For example+ the responses e v o k e d by NaG[ a n d HCI are s o m e w h a t s i m i l a r :11 bolh synafitic levels, W h e n the response of a n e u r o n to NaCI is vigorous, t h a l cell g e n e r a l l y re~pond~ well to HCI, and vice versa. T h e response IO sucrose, on the o t h e r b a n d . does g e l a p p e a r (o correlate with /hat to NaCI or HCI at e i t h e r synaptic level. C o m p o u n d s with v e l y s i m i l a r lilsles, like NaCI ~lnd NaNO:I (see Fig. IC), produce v e r y similar patterns of acfivd y across both p o p u l a l i o n s of cells (Fig. 4). T h e degree of similarity in t h e s e :lcross-nemon p a u e r n s of a c l i v i t g can be quantified by the across-neuron correlation b e t w e e n the firing r a t e s evoked by a p a i r of stimuli ncross all the n e u r o n s [3,8], T h a t is, i f Iwo compounds e v o k e e x a c t l y the s a m e response in all o f Ihe neurons, the c o r r e l a l i o n in t h e i r firing r a t e s across all the cells would be perfect. Across-neuron c o r r e l a t i o n s ( S p e a r m a n rbo) w e r e calculated for all pairs o f stimuli by c o r r e l a t i n g the n u m b e r of impulses e v o k e d in 5 sec across all 30 neurons. T h e s e across-neuron correlation coefficlenls, w h i c h m e a s u r e the similarity in the p a R e r n s of activity produced across these populations of cells, a r e pre-

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TABLE I MEAN S31MULUS UNCERrAINVY FQ{~ BEST S'I'I~,IULUS CAa EOORtE$ OF N ~ U R O N S [N I}IE N'[S AND PB PeNS Synapdc level NTS Pb pon~

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gustatory n e u r o n s [3, 5 . 6 . 7.81, Iben c o m p o u n d s w i t h similar tastes should e v o k e s i m i l a r patterns of a c t i v i l y a n d the patlerns e/Jelled by compounds with different tastes should be q u i t e distinct. A c o m p a r i s o n o r the b e h a v i o r a l similarity coefficients for t h e ten stimuli used in l h e p r e s e n t s~udy Io the across-neuron c o r r e l a t i o n s a m o n g Ihese stimuli should indieltle the degree to w h i c h the across-neuron p a t t e ~ s o f activity c a n a c c o u n t for t h e t a s t e similarities a m o n g these compounds. Such a c o m p a r i s o n b e t w e e n t h e b e h a v i o r a l and neural m e a s u r e s o f s i m i l a r i t y for n e u r o n s in the h a m s t e r N T S is s h o w n in Fig. 5. T h e b e h a v i o r a l similarity profiles for e a c h of the ten stimuli are s h o w n by the solid lines, indicating the d e g r e e to w h i c h these stimuli taste a l i k e to hamsters. T h e across-neuron c o r r e l a t i o n coefficients b e t w e e n all stimulus pairs a r e s h o w n by t h e dashed lines as correlational profiles for e a c h stimulus. T h e r e f o r e , a comparison of l h e s e t w o profiles for e a c h c o m p o u n d reveals b o w w e l l the across-neuron p a t t e r n s of activity correspond to t h e per-

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BRAINSTEM CORRELATES OF GUSTATORY SIMILARITY ceived s i m i l a r i t i e s a m o n g these stimuli. A s m a y be seen in Fig. 5, the across-neuron correlational profiles in t h e N T S a r e quite s i m i l a r to ~he b e h a v i o r a l profiles. If t w o c o m p o u n d s are j u d g e d Io h a v e similar tasles (e.g.. NaCI a n d N a N O:~) the across-neuron c o r r e l a t i o n coefficienl for t h a l p a i r of stimuli is close to + ] . 0 . w h e r e a s stimuli with l o w b e h a v i o r a l coeffieienls (e.g., sucrose a n d NaC[) h a v e v e r y l o w across-neuron correlation coefficients, i.e.. t h e i r across-neuron p a t t e r n s of activity are quite different (see also Fig. 4). T h e m a j o r departure From e x c e l l e n t fits b e t w e e n t h e s e t w o m e a s u r e s is in the g r e a t e r neural similarities a m o n g Ihe salts and acids t h a n would be e x p e c t e d from the b e h a v i o r a l data. F o r e x a m p l e , NaCI and NaNO:I are not j u d g e d to t a s t e similar to HCI and tartaric acid, although all of l h e s e c o m p o u n d s g e n e r a t e s o m e w h a t s i m i l a r patterns of neural activity across these N T S cells. T h e o t h e r sahs (NH~CI, CaCI~. a n d MgSOL) a r e positioned on this figure (both o n Ihe abscissa and in the ordering o f their profiles) in o r d e r of decreasing similarity IO N a C h If these sails a r e b e h a v i o r a l l y similar to NaC[ (e,g,, NH,CI) t h e y correlate too h i g h l y w i l h the acids, but if they are jtldged to laste m o r e )ike HCI (e.g., CaCI~ and MgSO.) t h e y are n e u r a l l y m o r e s i m i l a r 1o N a e l {hart w o u l d be predicted by the b e h a v i o r a l d:lta. T h e o n l y o t h e r e x c e p t i o n to this good fit b e t w e e n the n e u r a l and b e h a v i o r a l d a t a is the case of tartaric acid. w h i c h appears to h a v e a " s w e e t " componenl, as it is perceived by Ihese a n i m a l s to be solneWhat similar to b a t h sucrose and d l - a l a n i n e T h e r e is virtually no simdari~y, h o w e v e r , in the ~lcross-neuron p a t i e n t s of activity g e n e r a t e d by tartaric acid and these s w e e t - t a s t i n g compounds. T h e retafionship b e t w e e n the b e h a v i o r a l simiblrily profiles and rile across-neuron c o r r e l a t i o n s for cells in the Pb puns are s h o w n ill Fig. 6. In c o m p a r i s o n to the across n e u r o n corre~afions in Ihe NTS. w h i c h a r e often close to 0.0, but n e v e r n e g a l i v e , tbere are a n u m b e r of n e g a t i v e acloSSneuron correlations in the puns, mosl often i n v o l v i n g sfinmli j u d g e d to be bi(ter b y m a n (i.e.. QHCI a n d MgSO 0. With the exception of tile QHCI correiafions, these n e u t a l correlaIiomd profiles from the p o n l l n e cells fit the b e h a v i o r a l d a l a as well as those f r o m N T S cells. T h e across-neuron corre/a l i o n s for Q H C I . h o w e v e r , appear to be the m k r o r i m a g e of Ihe b e h a v i o r a l profile. T h e m o r e a c o m p o u n d laSleS ~ike QHC} Io these a n i m a l s the m o r e n e g a l i v e the across n e u r o n correlation ( Q H C I x M g S O 4 , r h o = - 0 . 3 8 ) , w h e r e a s Ihe m o r e different the lasle, ~he h i g h e r Ihe neural correlafion (QHCl• r h o - +0.21). As in the N T S , t h e r e is t h e t e n d e n c y for sahs and acids to s h o w g r e a t e r n e u r a l than b e h a v i o r a l similarity, a n d t h e r e is also no across-neuron c u r relation b e t w e e n t a r t a r i c acid a n d the s w e e t - t a s t i n g stimuli, as might be e x p e c t e d from the b e h a v i o r a l similarity coefficients a m o n g these compounds. DISCUSSION T h e present investigation o f the relationship b e t w e e n gustatory physiology a n d b e h a v i o r has focused r l h e h a m s t e r ' s g e n e r a l i z a t i o n of the l e a r n e d a v o i d a n c e of o n e s t i m u l u s to others w i t h s i m i l a r Iasles. T h e distinction b e t w e e n g e n e r alization a n d discrimination m a y be i m p o r l a n t h e r e in that t w o c o m p o u n d s t h a i a r e p e r c e i v e d to b e similar in this gene r a l i z a t i o n task m i g h t actually be quite discriminable i f the behavioral p r o c e d u r e w e r e different. For e x a m p l e , Q H C I a n d MgSO~ g e n e r a l i z e to o n e a n o t h e r q u i t e strongEy a n d s h o w s i m i l a r b e h a v i o r a l profiles (Fig. 5), a h h o u g h to m a n QHCI is perceived to be p u r e l y bitter a n d M g S O t to be par-

daily soul as well as briter 116]. Whether there is a species difference here might be furdler clarified by a behaviolal task r e q u i r i n g t h e discrimination b e t w e e n Q H C [ a n d M g S O t r a t h e r t h a n the g e n e r a l i z a t i o n b e t w e e n t h e m . N e v e r t h e l e s s , ~he g e n e r a l i z a t i o n o f a conditioned taste a v e r s i o n appears Io be a good m e i l s u r e o f l a s t e slnlilarity for s e v e r a l reasons. First. c o m p o u n d s that h a v e b e e n s h o w n to h a v e s i m i l a r tastes to rats (e,g., CltC]~ and N H , C I ) using apperifive operant p r o c e d u r e s ] 191 a l e seen to h a v e simlhtr b e h a v i o r a l profiles t'or h a m s t e r s using the present taste a v e r s i o n procedure (Fig. 5). Second, t h e r e is titrie o r no e v i d e n c e in Ihe present d a t a t h a i t h e s e a n i m a l s m e r e l y g e l l e n d l z e Io novel compounds 121. but r a t b e r that t h e y reslricl Iheir g e n e r a l i z a t i o n to t h o s e c o m p o u n d s w i t h s i m i l a r tasles. For e x a m p l e . Ihe g e n e r a l i z a f i o n function for N a C I s h o w n in Fig. IA demonstrates t h a t lhece is only g e n e n d i z a t i o n b e t w e e n NaC[ and the o t h e r s a b s and thai aninluls do nol genelTillze to rile o t h e r c o m p o u n d s simply because Ihey Die ull fnnrilJal. T h e hick o f u n e o p h o b i a Jn this s d u a d o n is nlosI fikely title Io the 471/:-br w a t e r d e p r i v a t i o n imposed before the test session, fi has b e e n recenriy s h o w n in the ral u s i n g v e l y simihu" p r o c e d u r e s that the anhllu] will g e n e r a l i z e Io taste m i x l u r e s strictly on tile basis of the c o n c e n t r a t i o n o f the conditioned s d m u l u s in Ihe m i x t u r e [381. Although h a m s t e r s h a v e beer. s h o w n to g e n e r a l i z e only Io the novel c o m p o n e n t ill a m i x e d conditioned stimulus 1241. Ihus d e m o n s l r a l i n g that Ihey do no/ lleqldre a n a v e r s i o n to Ibe filmiliar e o n l p o n e n l , t h e y do nol appear to g e n e r a l i z e from a conditioned taste aversion Io a n o l h e r s t i m u l u s simply because it is novel (Fig. I), T h u s the t a s t e a v e r s i o n procedures used ill d~e present study Elppear to p l o v i d e a scale of perceived taste shniinrity a m o n g t h e s e gustatory stimuli. T h e slmiblrity in the b e h a v i o r a l and neural categorizafiml of rilese g u s t a t o r y Slimuli (Figs. 5 and 6) is q u i t e striking. particularly in fight o f tbe l i m i l a t i o n s i n h e l e n t in the m a n l i e r in w h i c h these neural d a l a h a v e been a m d y z e d . First, the neural r e s p o n s e flleagllFC was simply a c o u n l of tile n u m b e r of impulses in Ibe first five sec of the response, As may be seen in Fig. 3, I h e r e are temporal variations in the responses to these s d m u l l during Ihis 5-see period, w h i c h cotdd bc involved in the coding of g u s t a l o r y q u a l g y [18, 25, 311. F u r t h e r , it has been shown that peripheral taste fibers in the rat a r e e x t r e m e l y sensilivr to t h e rate of stimulus onset 134 I, and Ihat the flow r a t e of a t a s t e s t i m u l u s can a)so af[ccl Ihe response of h a m s t e r N T S n e u r o n s [391. G i v e n t h a i g u s t a l o r y n e u r o n s a r e particularly s e n s i l l v e to changing sfimufi, t h e use of a constant flow across an i m m o b i l e Iongue is v e r y unlike the situation t h a t w o u l d o c c u r in a b e h a v i n g animal ([2, 13. 301 It is possible, for e x a m p l e , t h a t these ratesensitive n e u r o n s in the g u s t a t o r y system m i g h l he phaselocked in t h e i r responses to the licking b e h a v i o r of the ilnlreal in a simlrar m a n n e r to n e u r o n s in the h a m s t e r ollhclory bulb, w h i c h h a v e b e e n shown to respond to odors in syne h r o n y with the a n i m a l ' s i n h a l a t i o n cycle 1151. ]n spite of these limitations, these d a l a from an a c u t e a n e s l b e b z c d p r e p a r a t i o n q u i t e closely a g r e e with the b e h a v i o r a l categorlzafion o f t h e s e s g m u l i . This parallel b e l w e e n n e u r a l a n d b e h a v i o r a l m e a s u r e s of t a s t e similarity suggests that the g u s t a t o r y i n f o r m a t i o n from the a n t e r i o r portion of the t o n g u e is sufficient for b e h a v i o r a l j u d g m e n t s o f t a s l e quality. It has b e e n shown in h u m a n gsychophysical studies that e s t i m a l e s o f tasle i n t e n s i t y for q u i n i n e a r e readily o b t a i n a b l e f r o m s t i m u l a t i o n o f Ihe anterior portion o f ~be tongue [1,331, a n d that the threshold for QHCI is a c t u a l l y l o w e r for Ihe fungiform filan for the clr-

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BRAINSTEM CORRELATES OF GUSTATORY SIMILARITY

c u m v a g a t e papillae I l l . T h u s . the input f r o m the a n t e r i o r portion o f the tongue is sufficient for h u m a n j u d g e m e n t s o f bitterness. ] ' h e close fit b e t w e e n the b e h a v i o r a l similarity coefficients f o l Q H C I and the across-neuron correhttions bet w e e n QHCI a n d the o t h e r stimuli for N T S cells (Fig. 5), suggesls t h a t t h e neural i n p u l from the c h o r d a t y m p a u i n e r v e to the N T S is at least sufficient for j u d g e m e n t s of l a s t e sindlarlty for bitter-lasting stimuli. H o w e v e r , the nnimId's lotal g u s t a l o r y input most likely provides u m o r e c o m p l e t e sensory message. T h e r e a r e m a n y m o r e Q H C l - b e s t cells a m o n g rat g/ossopharyngeal neurons than in e i t h e r the rat or h a m ster chorda t y m p a n i n e r v e 124}. F u r t h e r . s o m e tnsle responsive cells in both the N T S of Ihe cat [ 14] and ~he Pb pOllS of Ihe ral ~23} h a v e b e e n s h o w n to r e c e i v e c o n v e r g i n g i n p m lhom both l h e fronl and back of t h e tongue. T h e r e f o r e . an analysis o f n e u r o n s from ~lcross Ihe u n i m a r s e n t i r e r e c e p t i v e field might provide an e v e n better fi~ ~o Ihese b e h a v i o r a l me:tsures o f taste sinlilarily. T h e a g r e e m e n t b e t w e e n the across n e u r o n p~ltlerns o f a c livi~y, as m e a s u r e d by the a c r o s s - n e u l o n c o r r e l a t i o n coefficients, a n d file b e h a v i o r a l data, w h i c h is really q u i t e good for NTS cells (Fig. 5). appe:~rs to d e t e r i o r a t e s o m e w h a ( in the Ph pon~ine cells, p a r l i c u l a l l y for Q H C I (Fig. 6). T h e r e is :~ deftnile change in t h e across-neuron correJations b e t w e e n QHC1 a n d the o t h e r stimuli b e t w e e n the N ' r S (Fig. 5). w h e r e the across-neuron c o r r e g n i o n s and Ihe b e h a v i o r a l similarity profiles for QHCI a g r e e subslanlhdly, lind the Pb puns (Fig. 6). In ~he Pb puns t h e l e appear~ ~o be a reciprocal relntionship belWeen heh~lviola] and neul'a) me~lsules of sinlilari)y for Q H C h T h e occurrence of Ihese n e g a l i v e across-neuron correlalions inlay w e l l renect the facl thnl m a n y of the responses to QHCI in the Ph puns appear ~o h e response decrements r a t h e r l h a n exci~:~tory responses (see Fig, 41. Thls peculiar rekttionship b e t w e e n QHCI a n d these o t h e r stimufi is difficull to interpret, a h h o u g h il is consistent with Ihe reflexive responses to QHCI and the o l h e r basic sfimufi s h o w n . by the ra~ I f i l l T h e m i m e l i c responses to sucrose. N a C l and HCI are all quite similar and distinctively different from {he response pattern following QHCI s t i m u l a t i o n , F u r t h e r . the neural substrale for these reflexive responses lies in Ihe b r a i n s t e m , since chronic d e c e r e b r a ( e rats ~how n o r m a l mimetic response p a t t e r n s [11]. Since Q H C ) elicits a sel of motor responses qui~e different from (hose e v o k e d by ~he o l h e r basic laste c o m p o u n d s , it w o u l d not be surprising if the processing of g u s t a t o r y input by neurons {11s o m e level o f l h e b m i n s l e m w e r e s o m e w h a t distinct for Q H C I . It is possible Ihat the d e c r e m e n t a l Q H C I responses in t h e Pb p u n s might play some role in this sort of reflexive behavior. T h e across-neuron c o l r e l a t i o n eoefficieht is a quantification of the similarity o f the patterns of a c t i v i t y g e n e r a t e d by t w o stimuli across a population of neurons. This pattern theory of taste q u a l i t y coding, first proposed by Pfaffmann [27.281 and further e l a b o r a t e d by Erickson [3, 5, 6, 7, 81, is well supported by t h e relationships b e t w e e n the b e h a v i o r a l similarity functions a n d Ihe neural c o r r e l a l i o n a l profiles for N T S cells (Fig. 5), a n d for Pb pontine ceils except for t h e correlations i n v o l v i n g Q H C I (Fig, 6). A n o t h e r v i e w of laste quality coding a s s u m e s l h a t e a c h n e u r o n carries i n f o r m a t i o n a b o u t o n l y o n e t a s t e q u a l i t y , given by its m o s t effective s t i m u l u s [24.29]. This labelled-line t h e o r y , for e x a m p l e . would argue ffial if a n e u r o n is driven best b y sucrose t h a t fls activity signals " ' s w e e t n e s s " no m a i l e r h o w it is evoked. According to a labelled-line notion, the a c t i v i t y in " s w e e t . " "'salty,'" " s o u r , " or " b i t t e r " n e u r o n s c a n r e p r e s e n t t h e taste quality of a c o m p o u n d . T h e r e f o r e , a c t i v i t y in sucrose-best

cells should correspond to the p e r c e i v e d " s w e e t n e s s " of e a c h c o m p o u n d , ~hat in NaCl-best cells to the " s a l t l n e s s , " a n d the respo~ses in HCI-besl cells should reflect the " s o u r hess'" of e a c h compound. To t h e s e h a m s l e r s , the perceived ' * s w e e t n e s s , " " s a l t i n e s s . " or " s o u r n e s s " of t h e s e stimull should correspond to how similar each is judged Io be to sucrose, N~ICI o r HCI. A t l e l n p t s to decide b e l w e e n these t w o theol'etic~d approaches h a v e been difficult, since Ihe m u i d p l y - s e n s l t l v e taste n e u r o n s ( F i g . 4) can be treated w i l h i n e i t h e r Iheoretical lhlmlework. A c o m p a r i s o n or these t w o t h e o r e t i c a l a p p r o a c h e s Io u n d e r s t a n d i n g the role of l a s l e he,irons mz~y be seen in Fig. 7, i n Fig. 7A the acloy;s-neuron correhldomd profiles (from Fig. 5) for StlCrose. N a C L a n d HCI a r e s h o w n Idasfied lines) in c o m p a l i s o n lo the behavioral s i m i l a r i l y profiles (solid lines) for t h e s e stimuli, T h e dashed lines in Fig, 7B show the m e a n imptdses/5 see e v o k e d by e a c h or the ~en stimufi in N T S cells ch~ssified as sucrosebest. NaCI-best lind HCI-best, d e p e n d i n g on w h i c h of tile four basic stimuli (sucrose, N a C L HCI or QHC/~ elicited file grenlest response, thus provhfing neural response profiles fol ',~ese quality specific netlrgt] **channels" [24.29]. T h e measUl'e o f the fit b e l w e e n I he neural :u/d b e h a v i o r a l daIa is g i v e n by the Pearson product-nJomenl correlation coefficienl for e a c h pair of profiles. If quulily is coded by ~clivily in these specific Challflgls, activity in sucrose-besl cells should correspond to the " ' s w e e t n e s s " of e a c h con}pound, i.e., to its porceived s i m i l a r i t y Io s u c l o s e As m a y be seen in Fig, 7. bolh t h e acl'oss-neuron p~lltel'ns of a c t i v i l y und Ihe ~lctivily in Ihese specific u e u l a t channel~ in fllc N T S correspond fidrly w e l l lo the b e h a v i o r a l simihlrity a m o n g Ihese compounds, "lhese s a m e lypes o r d a i n nre s h o w u for Pb pontine cells in Fig. 8. T h e across-neuron corl.ehlfion~d profiles are ngaJn s h o w n in Fig. 8A in compolison to the b e h a v i o r a l s i m i l a r i l y functions a n d the u c t i v h y in sucrose-. NaCI- lind HCl-best cells is s i m i l a r l y depicted in Fig. 8/3. A g u i n Ihe ilCl'OSsn e u r o n p a t t e r n s o f a c l i v i t y a g r e e fuir[y welt with the behavioral data, :is does tile ac~ivily in NaCI- and HCI-hesl neurons. H o w e v e r . Ihe responsiveness of the sucrose-best cells in Ihe Pb puns is much too broad to accounl J'Ol" Ihe b e h a v i o r a l specifieily of file sucrose g e n e r a l i z a t i o n filnclion, This atatisticaJly ,signlficant i n c r e a s e in the breadth of res p o n s i v e n e s s o r s u c r o s e - b e s t cells m a y idso be seen in Fig, 4 and T a b l e I. T h e m e a n responses to N a C L NaNO:~, CaCl~ and HCI ~lre aft gre~llel" in Ihese cells Iharl the m e a n response to dl-ahminr w h i c h is perceived to h e q u i t e similar to sucrose by these animals, As in the sucrose-best cells in ~he NTS, I h e r e is virtually no l e s p o n s e to Inrl~lric acid in these n e u r o n s t h a t could neeount for t h e b e h a v i o r a l similnfily of tnrtaric acid and sucrose. In general, e i l h e r an across-fiber pattern or a labelled-line notion a b o u t l a s t e quality coding could a c c o u n t for t h e perceived s i m i l a r i t i e s a m o n g Ihese ten stimuli, a l t h o u g h the responsiveness o f sucrose-best cells in the Pb puns is m u c h too broad to support the idea of a specific n e u r a l c h a n n e l for *'sweetness" ~1{ this level. A n a s s u m p t i o n t h a i underlies the consideration of the roles or taste-responsive n e u r o n s in the coding of l~lsle quality is t h a t all recorded n e u r o n s are i n v o l v e d in the proc* essing o f i n f o r m a l i o n i m p o r t a n t for sensory e x p e r i e n c e . This a s s u m p t i o n of h o m o g e n e i t y of function m a y nol be a p p r o p r i a t e in t h e central n e r v o u s system, w h e r e these cells m a y m e d i a t e functions o t h e r than g u s t a t o r y sensation a n d w h e r e t h e functional orguniza~ion a m o n g taste-responsive n e u r o n s is o n l y b e g i n n i n g to be understood 12i, 22, 23}. A s all e x a m p l e of t h e potential c o m p l e x i t y 6f ~his system, it has b e e n shown t h a t s o m e taste-resoonsive n e u r o n s in the r;ll

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fftG, 7. Conlp:wisml nf the fits belween behavioral tsolid lines) anti neural (NTS) dala tdashed linesl fer two different hypotheses about gu+tt~t +t, qtl~+~[Ivc~+~l$1g ~ Across-he iron r tt o~s imeng he 0 stimul and s icrose (top) NaCI Imiddle and HCI (bottom. compared It+ behux'i0ral ximilarity coemeiel~ts, 13: R e ~ l l s e s (mean impulses/5 scr to each or ihe ]o +linluli in sucrose-best (top), N+lCl-bc+t (middle) and b/Cl-hcst (llo[torll] cell+ h~ the tq'rs, r to beh~l~iond sintil+lr~ly coemcir Pr r's showIhe co~elation beh+een the two measures for erich set or profiles.

N T S receive c o n v e r g i n g input f r o m o d o n m l * r e s p o n s l v e Irlgeminal cells t40I. l ' h e ~ l e of the r e l a t i v e l y n a r r o w l y IIIned StlCrOSe- a n d QHCI-besl cells in the h a m s t e r N T S [391 could be h~ the i n n e r v a 0 o n of the inotor p+lthways i n v o l v e d in reflexive responses to t h e s e sl[nlul[, w h i c h (Ire k n o w n to exist ill the blmdnslem [111, T h e i11o1~ broad]y t u n e d sucr+se-best cells itl the pons (Figs. 4 a n d 8 B L w h i c h a r e too

broadly responsive to account for the b e h a v i o r a l g e n e r a l i z a lion a n m n g t h e s e stimuli, could be involved in coding l a s t e quality as part of a n across-fiber p a t t e r n (Fig, 8A) projecting rostral[y into the forebndn. H o w e v e r . the d e t e r m i n a t i o n of the role of single n e u r o n s in the coding of taste quality first r e q u i r e s a greaEer u n d e r s t a n d i n g of t h e functional o r g a n i z a tion a m o n g these l a s l e - r e s p o n s i v e ceils.

B R A I N S T E M C O R R E L A T E S O F GUSTAT~ )RY S I M I L A R I T Y

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gu~t;~tory qLlalit y coding. A; Across-nouron cor relalions among 1he 10 sllmull a~d sucrose {lop}, NaCI (m(ddle) und HCI {bottom), compale{I Io behavio~l similarity c~mciea~s. B: Responses (mean impulses/5 see) Io each of Ifle ]0 slimull in sucrosc~bc~l (lOp), NuCI-besl (middle) ~nd FIC~-best {bottom) cells in the Pb pons, compared to behavioral similarity coemcients. Pe~Lrsonr's shhow~fle correlation between ~hr two measures ['or each set of profiles,

372

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TRAVERS

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