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Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat
.Neuo~eie~ Ler~a:% 3 ~ (1992) 271-276 E[~qer/N~,zth-HsffasM S¢ieat;fic F~gNshers Ltd.
NPNTgAL MAPPgNG: DEI~INFflIVE DiSRUPT~iON N~ H : P P O C A ~ I P A L
ROBE~:T 2-; SUT~ERLAN~, BRYAN.KOLB ~ d ~AN Q. WHiSHAW
De~rt~Jent o f Ps2chOl~gy, Tke U~i~evMUOf Le~brMge, Le~brMge, A~&e~a, TIE ~M4 (C~sade) (Reeeived NaNh 8tii, 1982; Kgw:sed v-e:-glc~r~recei~:ed Aprii 27~h, ~. e~; Accepted M a y 24th, 1982)
Unlike norma~ ra~s, ;ats wi~h bilateral ~ i o ~ s in ekher :l~e hippocampus or m~dial frontal cor:ex did ~ot learn ~o swim from different diree:ions ¢oa hidden p!.~fform :ocated a~ a specific :~h:¢e.in a ~oom. Experimen:a} arid cgnieai evidence indicates ~rat a f:uaio-hipvscamr~: s~s~em may provide an in:esrated ne~roiogica~ basis for ;~ati~i represe.~:md~na: abigity.
C!inieal arid experimental re>or% on ~he effect of brain damage in h::ma~s ~nd ether m a m m a l s suggest that they have specia!izc~ aeurologiea} systems for ~e~ ~:mg and rerr~em~riag spatia] releresentations of aspects of thsir ¢~viro:~mentso For exampte~ human patiems who have andergone surgical excisioas of rigl~i hippocamp~ts or r~ght ffontat cortex exhibit a drar,a:~c deficit ia iea~ni~g co:-rc¢~ route~ in n~zes, regardless of the sensory moda~i:y af pre~,~en~atio~ I3, :Oi, and I¢,~io~u of the right parieto~oc-eipitaI cortex, if they are ¢:~e~sive, car: a!~:o i:'~_pai: maze learnir~g N, 33, 34]. There is an ex~:imen~ai iit~ra~rc demonstrating ~h¢ pNger~ee of impaired spatia~ ~ear~ieg in monkey:~ a:~d fa~s re!lowing b i i a ~ ai h:sic,r~5 f'7
ne'aror~ ae~ivffy in ~at i~iplaeNampus have diselos~:8 ~he pre~:eace of a large popu~at%a of ceils that ~elee~beely cha~age ~heir diNharge rage dep~r~dent upo~ the rat's F')sit~on ia an evirc~r~m~- {17° I t , 23,-27;~. ~ N ~ e ~he consistency of clinical and exp~,.~menta| res~l~s, the ~otion daa~ ~he hippecamp:~.s a~d frontal cortex have a selective iut~es~ in s~agial infor.ma~ier: has bee: cNled into questiom !nst~ad, :~: is suggested tha~. the~~. a;rue~ure~ a r e ievoived in 'working' ~'~emory and tempera! order:r~.g respectivegy [22,. 25~ ~:26~o ~ On ff~e~ views, ~he lcsion4ndaeed - ~ ~' , , spatial ~asks are eo~eemi~an~of more primary impairraea~s of working or temporal m e m o r i ~ We have smd ieJ r a s in a version of a a~:iqae test of s~asia: ioealiza~ion b2~,~ which is fr~ fro-m °~he w_. ~~ a.~:g ~ " or ~empora~ ~emor~ ~equirements implicit in soh':eg agernative 5pa~Ni i~robF.-m~ On: e.;ery ~riai ~:hrougho:~ ~;k(eIearn:ng ~?::asc ,)!" t~e e×pedme~a~ ~h~-faxJ~-m~gl~J{s:~ go a hi, dee p ~ t % r N whk:h is alway.'.; io~,~ed in the s,arae N a c e withlrL~d~e:reom a'~d ~Ii o; ~the.r~o~a~N: discda?}na~ive c~e~ in the r~4m .were aiwags p r e ~ t . ~: die same ~:~:.~ii~g~soThe:s, ~x:eurate orien~a:.ion doe~ "
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require reference memory but not r ~ m o r ] of cues that are relevam only for a particular trial (i.e. "~orking or temporaI memory). In this task, rats wi£h dare.go to ei~her the hippocami~us or medial frontal cortex show p~u~.~u~o~r' . . . . ~-~ 'e i m~,~.~ . ~ - ~.... . . , o. ~.~-¢ spatial maeping abitity. ." " ~ " ~- ? We trained rat5 to swim to ap.tafform ~hat w a ~ : N e d e ~ ; ~ t berber_h-the sarface o f cold water in a c~rcular p o o l The inside of the pool (di~cmeter 85 ~ , beigi~t 45 era) was paimed wNte and was fitted to 25 cm with lg~C wa~er° The h i d d ~ platform (l I × 12 c a ) w~c~painted white a~d ils wire mesh .~rfaee was approximately 1.5 cm below the water. A door, a window° a r ~ a l coamer, two ex~fimemers, several rows o~ empty cages, and a ceiling ligt~ fixture were visfNe from ~he pooi~ NEIk powder was dissolved in the water to render the platform invisible to a viewer at the water ~eve!. On a particular trial the rats began their search from one of four starting Iocation~ at the pool's perimeter and the order of starting locations was randomly assigned° The h~dden Natform r e m a / n ~ ~n the center of one quadrant of the pool ia *.he ~ m e plac~; within the testing roora %r the first 20 trials, thereafter (until trial 36) it was positioned in the cer~ter of the diagonally o p ~ s i ~ quadrant. On each trial we measured the latency to find the platform (maximum 120 secL the swim distance, the magnitude of the initial heading error after swimming approximately one body length (14 c a ) mid, on t~e fi~st trial after the platform was re-positioned (tria~ 21), the proportion of swim distance withh-~ the pre~ious[y correct quadrant. An experimenter at the p~o!'s edge r~orded the rat's swim path on a map of the poo~ a~d th:~se data were analysed on a APPLE gl magnetic graphics tablet. Thirty..eight ~ale, hooded Lo,~g-Eva~k, rats servee in this experiment. 'The tfippo~ campus was bilaterally damaged by electr:~ytie lesions (n ~-,4) or intra-hippocampa| microir~jections of kainic acid (q = 6), which preferentially d~troys the pyramidal cel~s ~,f ,..". ~J~,~ ... or co!chiei~e (n=6), which preferenfial~y destroy~ the dentate ,,r~,.~,., cel~s. Coetro~ rats (~=6) receded similar microinjeefi,~ns of ordy the neurotoxin vehicle solution. E~ee~rolytie 1esions (1,5 mA a~odat for ]5 see) and microiaject~ons (0.5 ¢~l/site) were made at three sims witNa each h i p ~ a m ~ u s . Coordinates were, with the skul! tevele~ between the bregma and l a m b ~ : for Kreb's solution control rats aw,~ kmnic acid (0.i ~,g/site) - (1) 2.5P, 2,3L, 3.3V, (2) 4.5P, 4.0L, 4.0V and (3} 5.0P, 4.~L, 7.5V; for the coich~eme (2 ~g/~ite) and electrot-ytie lesions - (~) 2.5P, I.OL, 3.9V, (2) 4,0P~ 2.0L, 4.8V and (3) 5.5P 4.4L, 5.7V. The solutions were in~ected throagh 30-gauge ~ta~nless steel tubing u~ir g a 5 CAHamilton microsyringe connected to an a~tomated pump. The medial flo~tal cortex was aspirated ~mder visua~ guidance (n = 8) and a second group of c~ntrol ra~ (n = 8) received ~he same surgical procedures without aspiration oi' ti~s~.~e, At the termination of testing at~ of the rats were sacrifice, ~he brains ,w~e processed, embedded in c¢Itoi~n~ and sectioned at 20 ~m. Every 5th,section t , ~ r o ~ ~he 1esCort w::s mounted a~8 ~he local:on of damage w a~ microscopically assessed in ,'reo--~ vio~e~;-~taiaed coronal se¢lions. After kain:~¢acid, over 90% of CA3-4 pyrami~N
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ra:~ actua~ty sq~ea~ed or dove under tb_e water as ~ as ff~y disc~wered that trio Nat~brm was not ~n its usm~i po.~tiom Imtiaiiy~ or~ce ~ rats ciimbed o.n,~o the p|at~brm_, they w o ~ d re~x up a~d turn around repeat~ly. With successive triag t~,~e freq~er~cy of rearing d ~ i n e d . Whe~ the platform w'~ re-p:~aitioncd, z~.~ng by coret'oi rats increased to its irdfialb" high ~ e q u ~ c y , Reari~zg by ~lie Ie$ion groups was unaffected by re-I~ifioning ~he platforrm During irdfiN ~ r n i n g veu¢.sirrdtar declines in the ini~.N~ beading error arm the swimming dis~v.:e were oh~..~ved: for the cor~tro~ g r o a n and rc-~sifiorfing the p~atform caused b ~ h of ~.hese measures across ttiais. The C A 3 - 4 and medial fromaI cortex ~eskm groups showed a sigrdficant linear decline in latency to find the Natforra. Both were skewer than the torero! grovps and neither demonstrater3 any change throug~h~at the experfiment in the magrdtude of their inifia~ heading error, nor did they show a preference for the previously correct quadrant when ti'm Natform was re-pcrsitioned. The A N O V A ir.dicated statistically significant changes across trial biocks for the C A 3 - 4 lesion rats N8,49) = t3.6, P < q . ~ l , and fc,r ~be medial frontal rats, F(8,55) = 7.8, P<0.0Oi. "the latter grou;~ was s~ower than their contmt group compared across aLi trial blocks, Nt,14) = 9.4, P<0.OI. P~t*ho¢ t~ts using Tukey's ~qethod at the 0.05 level of significance showed that the C A 3 - 4 ~esio~ group was slower than the Kreb's injected control grou~ only on the first 3 blocks of trials. T~e fact that the lesion groups were impaired on measures of swimming distance, quadrant pre%rence, and initiai heading error, makes unlikely any e×Na~atior~ of our latency data based upon a simpl~ problem in motor coordination or swimming s~eed. All of ~hese results are consistent w~th the interpretation that norma~ ra~; iv. this ~ask very readily learn, ia the absence of any l~ca~ cue% to swim direc.:~y to a particular place within the test room from ~everal difterent direcfio:~. Ra~s w~th damage ir~ hiprmcampus or medial frontal cortex do not have this spatial mapNng ability. We have atso found that rats with bflatera~ c|ectrolytic lesions in the habenuta, thalamus or amygdala, or bilateral suction ablatio~ of motor cortex, perform as well as control rats in this task. Since the water task does not have a working ~emory or temporal ordering requirement, it is unlikely that o u r deficit reflects an impairment in ,~ orking or temporal memories, it shou2d be noted that we have not tested these mfimals in a task that explicitly requires wor~ing memory or temporal mem~'y ability, so that we do not know whether, in addition to the spatial localization deficit, ~'heywould show impairments of t h ~ abilities. In a subsequent experiment [81, we have show~ that rats with unilateralhippecampal ablation are impaired in learning the wa,er task, but not in learning a version ~ff the 8-arm radial maze which contains an ~:xplicit working memory ~equiremeat [221. In other experhne~:~ts [26, 27], v,e have demonstrated that norton rats probably do u ~ visual cues fron ~, the test re-am to locate the platfc,rm. The modest improvement in the latency to fine! t~'~eplatform shown by the C~t3-4 and medial frontal cortex lesion rats may indkate that they can learn to use a non-mapping l ~ N i ~ t i o a strat%~], perhaps based u~on developing a more, efficient search pattern° We have found that
275
if ~he ~ecadon ~,i"~he-plae'orm is randomiy changed from trial to trial, normal rata do develop am effieiem non-mapNng localization strategy [27~. Given our Pmding of a simEar spatial mapping deficit after NppocampaI and medial [roetN damage, a~.:d the ctlnical reports that right hippocampal and fight froma~, da~n~ge cause simiNr spatial learni=g deficits in humans, we suggest that these s~ruet~ares form a fun, aionaRy int~rat~'a system for ~earnieg and using spatial r~presentaflons:0f a s s e t s of emdronments. Direct and indirect .anatomical linkages between these two structures which reign mediate such an integrative activity have been described [1,-3, 28]. The smC;y of brain-damaged rats in this task provides a useful model system for examining hypotheses that arise from the human clinicM neuropsychol~gical literature coneemi~ag the specific contributions of h~.ppocampus [12. 15, 28, 29], fronfal [8, 28] and pv'ieto~occipital cortex [8], and striatat motor systems [2], to spatial learning and memory. The authors are pleased to thank Richard Dyck for technical aasistance and Mrs. Adda Allen for typing the manuscript. The research was supported by Natural Science and Engineering Researck Council of Canada grants to the three authors. Preliminary reports of these data were made at the Annual Meetings of the Society for Neurosciences [8, 29], and a report of similar deficits in the water task after hippoeampa~ damage was made by Morris, et al. [13]. [ Bookstand, R.M., An autoracliographic examination of cortico-cortical a.~d svbconica] p~'ojectmns of the mediodor.~aVprojeetion (preDrmta~) rortex in the rat, J. comp. Neurol., ~84 {~979} 43-62. 2 Camp, D.M., Therrie~J, BOA.+ and Robin.~on, T.E., Spatial learning ability h ~e~ated to an endogeno~s asymmetry in the nigrostriatM dopamme system in rats, Neuroses. Abstr., 7 {198 ] } 455. 3 Corkm, S., Tactually-guided m;~ze ~earning in man: e~Tects o~ ur~ila~crat cord~ai e×d~ion~, and bilateral bippocampal lesions, Net~.eopsychol., 3 ( 1965} 339- 35 I. 4 D{va¢, I. and Diemer, N.H.~ Prefror~at system in the rat visualized by means of iabe}ed deo×ygtucose - further ev.~dence for hmctional heterogen.i~y of the neostria~um, J. temp. Neurol., 190 ~1980) I-!3. 5 Gotdsehmidt, R,B. and S~eward, O., Preferential neurotoxicity of colchicine for granule ceBs of the dentate gyru~, of the adult rat, Prec. nat. Acad. Scio U.S.A., 77 {!980) 3047-.305~. 6 Hecaen, H,, Tzortzis, C. and Rondel, P., Loss of topographic memory with learning deficits, Cortex, 16 (19gO) 525-542, 7 Hyvarinen, J. and Poranen, A., Function of the parietal associative area 7 as revealed from cc Hutar discharges h~ alert monkeys, Brain, 97 {1976} 673-692. 8 Koib0 B., Da~herland, R.J. arid Whishaw, I.Q., The rdative contribution of cortical site and side in the eontroI of pra×ie and spa:in[ behavior, Nearosci./~bstr., 7 (~9?A) 521. 9 Krettek, J,E. and Price, LL., The conical projections of the mediodorsa[ wacteus and adiacen~ tha~amie nuclei in the rat, .L zomp. Neurol., ~7t (!97% 157-[92. t0 M~ne~, B°, Visua~)'-guided n.aze icar;fi~,g it? maw ef~ev,:5 of b;la~era~ gip,~acaraf~ak bida~er~,1 ~r'.mta~ and un,iNtera] eerebrN lesiona, NeuropsychoL, 3 (;965~ 3|%.338. t I Mi51~tkir~,M, and Mater,inn, F.J., Nogo~patiat memory after _~e*ectiveprefronta~ !esions ir~ monkey;, Brak~ Re~., i43 ~197g) 3~3-323. 12 Morrh, RoG.M., Spadal l~-:a iza~ion doe~ not require the pre~er~ee of focal c~.~es, Learn° Mo~iva,Ao.~, 12 (iOggt 239-2(f0.
~6
memow.¢ d e ~ t ia ~t~ raL Ne~cacL At~tro,- l t {lt~I) 237. t a M,~rl~casde, V.B., T~e world ~c~nd us: m~ar~l c.az~rae~-_~ fumcfien~ for ~elec~vc m~tem.~o~. Ne~r~, R ~ . Pr~r~. ~ . , i4 (1976) 1-47.-- . . . . . . -
17 O°Kaf~, t., A review of ll~e ~ ¢ a m l ~ [ #~.,~ ee~,P=ogr._ Nc~r@i~L; 13 (t,~/i) 4i9-4}9. 18 O'Keefe, lo and Do~.rov~ky, l., Tire l'dppocampu~ ~s a spatiat map. P r e l i m } ~ evidemee fr-~muiah acti~F.y in tt',e free|y moving rat, Brain Res., 34 (i971) 171-175. : ~9.3'Keefe, J. w~d i~d.~l, L., The Hii~u)cam~ ~s a Cogn:tive Map, C'iaret~cna Pres~, Oxford; 1978. 20 O'Keege, J., NadeI, L., Kei~tley, $. and Kill D., Forrfix ~ i o m ~L,etively ~b~A~h #ace learnir~g in the rm, E~p, Ne~oL, 48 (1975} I52-16& 2t Okon, D.S., T~e fvr~cfion of septo-hipl~aca,_~pat cr~r~.do~ in sp~fiaily organized be~vLonr. I~ Functions of the Septo-Hippocampal S ~ e m , C~ba Foundation Symposium 58, Else'Aer/NorthHcA~and, New York, i978. 22 Ohot% D.S., ~ecker, £T. a ~ Handetmm'm, G.E., H~ppoe~mp~$, space, a~d ~ y , Behav. Brain $ci., 2 (~97~) 313-365. 23 Olto~, D.S., Branch, M. and Bes{, P.I., Spatia| correlates of hippocampal unit activity, Exp. NeuroL 58 {1978) 387-409. 24 Pohl, W., DissiPation of spatial d~cfiminatio~ deficit~ fo|low~ng fronta~ az~d ~k;~a~ ~e_c~onsin monkeys, £ eomp0 physiol. P~ychoi., 82 (t973) 227-239. 25 Pribram, ~.H., The primate frontal c o r t e x - enecufi,~eof ~ b~a~a, ~n K.H. PHbmm m~d A.R. Lurid (Eds.L Psychophysiotogy of the FtontM Lobe~, Ac~dem~c Pres~, New York, I973, pp. 293-3114. 26 Pribram, K.H., Plotkin, H,C,, Ander~o,h R.M. a ~ Leong, D., ~nformaio~ s o u r c e ~ in the ddayed ahe~nation zask for normal anc~ 'frontal' monkeys, Neurop~ychoL. ~5 (1977) 32f:--3~0. 27 }lanck, £B., Studk~s on single nenrons in dor~af hippoeampal formalior, and ~-pium in um~ralned rats, Exp. Neurof., 41 ({973) 461-555o 28 Sutherhmd, R.J., Kolb, B. and Whi~h~w, ~.Q., Neonatal 6-hydro,,y~opami~e administration elimina~.e.~ sparing of funclion atter ~eonatat frontal cortex damage, Ncurc~ci. Ab,tr., 7 {198|) 4{. 29 Sutherland, R.J., Whishaw, I.Q. and Kolb, ~., Abmoro,~ttid~s irr EF:G and zp~,iai p e r f o r m ~ following intrahippocam~z| injections of neurotoMns, Neurosci. Absm, 6 (t9~) 565~ 30 Suthertand, R.J., Whishaw, I.Q. ane v o ~ B., A behavioral analysis of ~patla] k~ca~izadon following electrolytic, kaina~e-, or colcbieinednduce~ damage ~o the hippocampat formation in the rat, t~ehav. Brain Res., in press, 31 Smherla~)d, R.J., Wh~shaw, i.Q. and Regel~r0 $.C., Chol~ner#c receptor bMcka:te impairs spatial localization in lhe rat, .L compo physloL Psyc~oi., in pre~s, 32 Swanson, L.Wo, A direc~ 9rejection from Ammoa's ho~n to prefrontal cortex in the ra~, Brain Re~., 217 {198~) 150-15~. 33 Wh~leley, A,M., and Warring~oa, E.K., Selective mpairmen~ of ~opog~aphica} memory.: a single case study, J. Neuro{. Neurosurg. Pyseh}at., 41 (t978~ 575-578. 34 Wholly, C.W.M and Newcombe, F., R.C. Oldfie d's sludy of visual and topographic dislurbances in a righ~ oecipito-i~a~ie).a! [esion of 30 year~ duration, Neuropsychot., l I (197~) 47~-475.
NPNTgAL MAPPgNG: DEI~INFflIVE DiSRUPT~iON N~ H : P P O C A ~ I P A L
ROBE~:T 2-; SUT~ERLAN~, BRYAN.KOLB ~ d ~AN Q. WHiSHAW
De~rt~Jent o f Ps2chOl~gy, Tke U~i~evMUOf Le~brMge, Le~brMge, A~&e~a, TIE ~M4 (C~sade) (Reeeived NaNh 8tii, 1982; Kgw:sed v-e:-glc~r~recei~:ed Aprii 27~h, ~. e~; Accepted M a y 24th, 1982)
Unlike norma~ ra~s, ;ats wi~h bilateral ~ i o ~ s in ekher :l~e hippocampus or m~dial frontal cor:ex did ~ot learn ~o swim from different diree:ions ¢oa hidden p!.~fform :ocated a~ a specific :~h:¢e.in a ~oom. Experimen:a} arid cgnieai evidence indicates ~rat a f:uaio-hipvscamr~: s~s~em may provide an in:esrated ne~roiogica~ basis for ;~ati~i represe.~:md~na: abigity.
C!inieal arid experimental re>or% on ~he effect of brain damage in h::ma~s ~nd ether m a m m a l s suggest that they have specia!izc~ aeurologiea} systems for ~e~ ~:mg and rerr~em~riag spatia] releresentations of aspects of thsir ¢~viro:~mentso For exampte~ human patiems who have andergone surgical excisioas of rigl~i hippocamp~ts or r~ght ffontat cortex exhibit a drar,a:~c deficit ia iea~ni~g co:-rc¢~ route~ in n~zes, regardless of the sensory moda~i:y af pre~,~en~atio~ I3, :Oi, and I¢,~io~u of the right parieto~oc-eipitaI cortex, if they are ¢:~e~sive, car: a!~:o i:'~_pai: maze learnir~g N, 33, 34]. There is an ex~:imen~ai iit~ra~rc demonstrating ~h¢ pNger~ee of impaired spatia~ ~ear~ieg in monkey:~ a:~d fa~s re!lowing b i i a ~ ai h:sic,r~5 f'7
ne'aror~ ae~ivffy in ~at i~iplaeNampus have diselos~:8 ~he pre~:eace of a large popu~at%a of ceils that ~elee~beely cha~age ~heir diNharge rage dep~r~dent upo~ the rat's F')sit~on ia an evirc~r~m~- {17° I t , 23,-27;~. ~ N ~ e ~he consistency of clinical and exp~,.~menta| res~l~s, the ~otion daa~ ~he hippecamp:~.s a~d frontal cortex have a selective iut~es~ in s~agial infor.ma~ier: has bee: cNled into questiom !nst~ad, :~: is suggested tha~. the~~. a;rue~ure~ a r e ievoived in 'working' ~'~emory and tempera! order:r~.g respectivegy [22,. 25~ ~:26~o ~ On ff~e~ views, ~he lcsion4ndaeed - ~ ~' , , spatial ~asks are eo~eemi~an~of more primary impairraea~s of working or temporal m e m o r i ~ We have smd ieJ r a s in a version of a a~:iqae test of s~asia: ioealiza~ion b2~,~ which is fr~ fro-m °~he w_. ~~ a.~:g ~ " or ~empora~ ~emor~ ~equirements implicit in soh':eg agernative 5pa~Ni i~robF.-m~ On: e.;ery ~riai ~:hrougho:~ ~;k(eIearn:ng ~?::asc ,)!" t~e e×pedme~a~ ~h~-faxJ~-m~gl~J{s:~ go a hi, dee p ~ t % r N whk:h is alway.'.; io~,~ed in the s,arae N a c e withlrL~d~e:reom a'~d ~Ii o; ~the.r~o~a~N: discda?}na~ive c~e~ in the r~4m .were aiwags p r e ~ t . ~: die same ~:~:.~ii~g~soThe:s, ~x:eurate orien~a:.ion doe~ "
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Ltdo
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require reference memory but not r ~ m o r ] of cues that are relevam only for a particular trial (i.e. "~orking or temporaI memory). In this task, rats wi£h dare.go to ei~her the hippocami~us or medial frontal cortex show p~u~.~u~o~r' . . . . ~-~ 'e i m~,~.~ . ~ - ~.... . . , o. ~.~-¢ spatial maeping abitity. ." " ~ " ~- ? We trained rat5 to swim to ap.tafform ~hat w a ~ : N e d e ~ ; ~ t berber_h-the sarface o f cold water in a c~rcular p o o l The inside of the pool (di~cmeter 85 ~ , beigi~t 45 era) was paimed wNte and was fitted to 25 cm with lg~C wa~er° The h i d d ~ platform (l I × 12 c a ) w~c~painted white a~d ils wire mesh .~rfaee was approximately 1.5 cm below the water. A door, a window° a r ~ a l coamer, two ex~fimemers, several rows o~ empty cages, and a ceiling ligt~ fixture were visfNe from ~he pooi~ NEIk powder was dissolved in the water to render the platform invisible to a viewer at the water ~eve!. On a particular trial the rats began their search from one of four starting Iocation~ at the pool's perimeter and the order of starting locations was randomly assigned° The h~dden Natform r e m a / n ~ ~n the center of one quadrant of the pool ia *.he ~ m e plac~; within the testing roora %r the first 20 trials, thereafter (until trial 36) it was positioned in the cer~ter of the diagonally o p ~ s i ~ quadrant. On each trial we measured the latency to find the platform (maximum 120 secL the swim distance, the magnitude of the initial heading error after swimming approximately one body length (14 c a ) mid, on t~e fi~st trial after the platform was re-positioned (tria~ 21), the proportion of swim distance withh-~ the pre~ious[y correct quadrant. An experimenter at the p~o!'s edge r~orded the rat's swim path on a map of the poo~ a~d th:~se data were analysed on a APPLE gl magnetic graphics tablet. Thirty..eight ~ale, hooded Lo,~g-Eva~k, rats servee in this experiment. 'The tfippo~ campus was bilaterally damaged by electr:~ytie lesions (n ~-,4) or intra-hippocampa| microir~jections of kainic acid (q = 6), which preferentially d~troys the pyramidal cel~s ~,f ,..". ~J~,~ ... or co!chiei~e (n=6), which preferenfial~y destroy~ the dentate ,,r~,.~,., cel~s. Coetro~ rats (~=6) receded similar microinjeefi,~ns of ordy the neurotoxin vehicle solution. E~ee~rolytie 1esions (1,5 mA a~odat for ]5 see) and microiaject~ons (0.5 ¢~l/site) were made at three sims witNa each h i p ~ a m ~ u s . Coordinates were, with the skul! tevele~ between the bregma and l a m b ~ : for Kreb's solution control rats aw,~ kmnic acid (0.i ~,g/site) - (1) 2.5P, 2,3L, 3.3V, (2) 4.5P, 4.0L, 4.0V and (3} 5.0P, 4.~L, 7.5V; for the coich~eme (2 ~g/~ite) and electrot-ytie lesions - (~) 2.5P, I.OL, 3.9V, (2) 4,0P~ 2.0L, 4.8V and (3) 5.5P 4.4L, 5.7V. The solutions were in~ected throagh 30-gauge ~ta~nless steel tubing u~ir g a 5 CAHamilton microsyringe connected to an a~tomated pump. The medial flo~tal cortex was aspirated ~mder visua~ guidance (n = 8) and a second group of c~ntrol ra~ (n = 8) received ~he same surgical procedures without aspiration oi' ti~s~.~e, At the termination of testing at~ of the rats were sacrifice, ~he brains ,w~e processed, embedded in c¢Itoi~n~ and sectioned at 20 ~m. Every 5th,section t , ~ r o ~ ~he 1esCort w::s mounted a~8 ~he local:on of damage w a~ microscopically assessed in ,'reo--~ vio~e~;-~taiaed coronal se¢lions. After kain:~¢acid, over 90% of CA3-4 pyrami~N
273
cells ~er¢ destr~
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Fig~ L The la~en.cy ~o hnd the h.id~en platform b: d,~
dier~ of suction remova~ of medial fronta~ corte:~o
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274
ra:~ actua~ty sq~ea~ed or dove under tb_e water as ~ as ff~y disc~wered that trio Nat~brm was not ~n its usm~i po.~tiom Imtiaiiy~ or~ce ~ rats ciimbed o.n,~o the p|at~brm_, they w o ~ d re~x up a~d turn around repeat~ly. With successive triag t~,~e freq~er~cy of rearing d ~ i n e d . Whe~ the platform w'~ re-p:~aitioncd, z~.~ng by coret'oi rats increased to its irdfialb" high ~ e q u ~ c y , Reari~zg by ~lie Ie$ion groups was unaffected by re-I~ifioning ~he platforrm During irdfiN ~ r n i n g veu¢.sirrdtar declines in the ini~.N~ beading error arm the swimming dis~v.:e were oh~..~ved: for the cor~tro~ g r o a n and rc-~sifiorfing the p~atform caused b ~ h of ~.hese measures across ttiais. The C A 3 - 4 and medial fromaI cortex ~eskm groups showed a sigrdficant linear decline in latency to find the Natforra. Both were skewer than the torero! grovps and neither demonstrater3 any change throug~h~at the experfiment in the magrdtude of their inifia~ heading error, nor did they show a preference for the previously correct quadrant when ti'm Natform was re-pcrsitioned. The A N O V A ir.dicated statistically significant changes across trial biocks for the C A 3 - 4 lesion rats N8,49) = t3.6, P < q . ~ l , and fc,r ~be medial frontal rats, F(8,55) = 7.8, P<0.0Oi. "the latter grou;~ was s~ower than their contmt group compared across aLi trial blocks, Nt,14) = 9.4, P<0.OI. P~t*ho¢ t~ts using Tukey's ~qethod at the 0.05 level of significance showed that the C A 3 - 4 ~esio~ group was slower than the Kreb's injected control grou~ only on the first 3 blocks of trials. T~e fact that the lesion groups were impaired on measures of swimming distance, quadrant pre%rence, and initiai heading error, makes unlikely any e×Na~atior~ of our latency data based upon a simpl~ problem in motor coordination or swimming s~eed. All of ~hese results are consistent w~th the interpretation that norma~ ra~; iv. this ~ask very readily learn, ia the absence of any l~ca~ cue% to swim direc.:~y to a particular place within the test room from ~everal difterent direcfio:~. Ra~s w~th damage ir~ hiprmcampus or medial frontal cortex do not have this spatial mapNng ability. We have atso found that rats with bflatera~ c|ectrolytic lesions in the habenuta, thalamus or amygdala, or bilateral suction ablatio~ of motor cortex, perform as well as control rats in this task. Since the water task does not have a working ~emory or temporal ordering requirement, it is unlikely that o u r deficit reflects an impairment in ,~ orking or temporal memories, it shou2d be noted that we have not tested these mfimals in a task that explicitly requires wor~ing memory or temporal mem~'y ability, so that we do not know whether, in addition to the spatial localization deficit, ~'heywould show impairments of t h ~ abilities. In a subsequent experiment [81, we have show~ that rats with unilateralhippecampal ablation are impaired in learning the wa,er task, but not in learning a version ~ff the 8-arm radial maze which contains an ~:xplicit working memory ~equiremeat [221. In other experhne~:~ts [26, 27], v,e have demonstrated that norton rats probably do u ~ visual cues fron ~, the test re-am to locate the platfc,rm. The modest improvement in the latency to fine! t~'~eplatform shown by the C~t3-4 and medial frontal cortex lesion rats may indkate that they can learn to use a non-mapping l ~ N i ~ t i o a strat%~], perhaps based u~on developing a more, efficient search pattern° We have found that
275
if ~he ~ecadon ~,i"~he-plae'orm is randomiy changed from trial to trial, normal rata do develop am effieiem non-mapNng localization strategy [27~. Given our Pmding of a simEar spatial mapping deficit after NppocampaI and medial [roetN damage, a~.:d the ctlnical reports that right hippocampal and fight froma~, da~n~ge cause simiNr spatial learni=g deficits in humans, we suggest that these s~ruet~ares form a fun, aionaRy int~rat~'a system for ~earnieg and using spatial r~presentaflons:0f a s s e t s of emdronments. Direct and indirect .anatomical linkages between these two structures which reign mediate such an integrative activity have been described [1,-3, 28]. The smC;y of brain-damaged rats in this task provides a useful model system for examining hypotheses that arise from the human clinicM neuropsychol~gical literature coneemi~ag the specific contributions of h~.ppocampus [12. 15, 28, 29], fronfal [8, 28] and pv'ieto~occipital cortex [8], and striatat motor systems [2], to spatial learning and memory. The authors are pleased to thank Richard Dyck for technical aasistance and Mrs. Adda Allen for typing the manuscript. The research was supported by Natural Science and Engineering Researck Council of Canada grants to the three authors. Preliminary reports of these data were made at the Annual Meetings of the Society for Neurosciences [8, 29], and a report of similar deficits in the water task after hippoeampa~ damage was made by Morris, et al. [13]. [ Bookstand, R.M., An autoracliographic examination of cortico-cortical a.~d svbconica] p~'ojectmns of the mediodor.~aVprojeetion (preDrmta~) rortex in the rat, J. comp. Neurol., ~84 {~979} 43-62. 2 Camp, D.M., Therrie~J, BOA.+ and Robin.~on, T.E., Spatial learning ability h ~e~ated to an endogeno~s asymmetry in the nigrostriatM dopamme system in rats, Neuroses. Abstr., 7 {198 ] } 455. 3 Corkm, S., Tactually-guided m;~ze ~earning in man: e~Tects o~ ur~ila~crat cord~ai e×d~ion~, and bilateral bippocampal lesions, Net~.eopsychol., 3 ( 1965} 339- 35 I. 4 D{va¢, I. and Diemer, N.H.~ Prefror~at system in the rat visualized by means of iabe}ed deo×ygtucose - further ev.~dence for hmctional heterogen.i~y of the neostria~um, J. temp. Neurol., 190 ~1980) I-!3. 5 Gotdsehmidt, R,B. and S~eward, O., Preferential neurotoxicity of colchicine for granule ceBs of the dentate gyru~, of the adult rat, Prec. nat. Acad. Scio U.S.A., 77 {!980) 3047-.305~. 6 Hecaen, H,, Tzortzis, C. and Rondel, P., Loss of topographic memory with learning deficits, Cortex, 16 (19gO) 525-542, 7 Hyvarinen, J. and Poranen, A., Function of the parietal associative area 7 as revealed from cc Hutar discharges h~ alert monkeys, Brain, 97 {1976} 673-692. 8 Koib0 B., Da~herland, R.J. arid Whishaw, I.Q., The rdative contribution of cortical site and side in the eontroI of pra×ie and spa:in[ behavior, Nearosci./~bstr., 7 (~9?A) 521. 9 Krettek, J,E. and Price, LL., The conical projections of the mediodorsa[ wacteus and adiacen~ tha~amie nuclei in the rat, .L zomp. Neurol., ~7t (!97% 157-[92. t0 M~ne~, B°, Visua~)'-guided n.aze icar;fi~,g it? maw ef~ev,:5 of b;la~era~ gip,~acaraf~ak bida~er~,1 ~r'.mta~ and un,iNtera] eerebrN lesiona, NeuropsychoL, 3 (;965~ 3|%.338. t I Mi51~tkir~,M, and Mater,inn, F.J., Nogo~patiat memory after _~e*ectiveprefronta~ !esions ir~ monkey;, Brak~ Re~., i43 ~197g) 3~3-323. 12 Morrh, RoG.M., Spadal l~-:a iza~ion doe~ not require the pre~er~ee of focal c~.~es, Learn° Mo~iva,Ao.~, 12 (iOggt 239-2(f0.
~6
memow.¢ d e ~ t ia ~t~ raL Ne~cacL At~tro,- l t {lt~I) 237. t a M,~rl~casde, V.B., T~e world ~c~nd us: m~ar~l c.az~rae~-_~ fumcfien~ for ~elec~vc m~tem.~o~. Ne~r~, R ~ . Pr~r~. ~ . , i4 (1976) 1-47.-- . . . . . . -
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