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The Hippocampus and Pavlovian Fear Conditioning: Reply to Bast Et Al

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The Hippocampus and Pavlovian Fear Conditioning: Reply to Bast Et Al See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/11186221 The hippocampus and Pavlovian fear conditioning: Reply to Bast et al Article in Hippocampus · January 2002 DOI: 10.1002/hipo.10071 · Source: PubMed CITATIONS READS 21 41 3 authors, including: Stephan G Anagnostaras Michael Fanselow University of California, San Diego University of California, Los Angeles 286 PUBLICATIONS 4,968 CITATIONS 285 PUBLICATIONS 25,323 CITATIONS SEE PROFILE SEE PROFILE All content following this page was uploaded by Stephan G Anagnostaras on 23 June 2017. The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. HIPPOCAMPUS12:561–565(2002) TheHippocampusandPavlovianFearConditioning: ReplytoBastetal. StephanG.Anagnostaras,1 GregD.Gale,2 andMichaelS.Fanselow2 1DepartmentofPsychologyandCenterforBehavioral Neuroscience,EmoryUniversity,Atlanta,Georgia 2DepartmentofPsychologyandBrainResearchInstitute, UniversityofCalifornia,LosAngeles,California InarecentarticlethatappearedinHippocampus,wereviewedfindings futureworkintheareaofVHwillbeessentialtoour supportingamnemonicroleforthedorsalhippocampus(DH)inPavlovian understandingoftheneuralcircuitsinvolvedincontex- (contextualandtone)fearconditioning(Anagnostarasetal.,2001).Wealso tualfearconditioning: detailedaviewthathasemergedovertheyearsfromthisworkthatsuggests thatthehippocampusplaysahighlyselectiveroleintheacquisitionand 1.Complete,excitotoxichippocampallesionsabolish temporarystorageofcontextualrepresentations,asopposedtoarolein Pavlovianconditionedfreezing.Itisevidentfrom conditionalstimulus–unconditionalstimulus(CS–US)associationsorin severalstudiesthatcompletehippocampallesions,which permanentstorageforwhichtheamygdalahasbeenheavilyimplicated(Kim inratmemorystudieshaveonlybeendonewithexcitox- andFanselow,1992;PhillipsandLeDoux,1992;Youngetal.,1994;Maren ins,produceanonselectiveandnonspecificdeficitincon- andFanselow,1996;Marenetal.,1996,1997,1998;Anagnostarasetal., textualandtonefearconditioning,forbothrecentand 1999).BecausetheevidencethatDHlesionsproduceatemporallygraded remotefear.Inseveralstudiesusingkainite-colchicine retrogradeamnesiaselectiveforcontextualfearthataccordswellwithde- lesionsofthehippocampusinSutherland’slaboratory, clarativememorydeficitsinamnesichumans,wehavefurtherarguedthis thefindingsindicatesubstantialimpairmentsinremote maybeagoodmodelsystemwithwhichtostudythetransformationof andrecentfear,aswellassimilardeficitsinother memoryfromahippocampus-dependenttoahippocampus-independent taskssuchasthehidden-platformMorriswatermaze (cortical)state(i.e.,consolidation)(ScovilleandMilner,1957;Squire, (Weisendetal.,1996;Sutherlandetal.,2001).Indeed, 1992;SquireandAlvarez,1995;HodgesandGraham,1998;Squireetal., inourownwork,wehaverecentlyfoundthatcomplete 2001;Murreetal.,2001;Franklandetal.,2001). hippocampuslesionsproducedbyibotenicacidinthe InalettertoHippocampusregardingourrecentarticle,Bastetal.(2001b) mannerdescribedbyJarrard(1989)produceasevere expandonourreviewtodiscusstheirrecentdata(andthedataofothers), temporallyungradedretrogradeamnesiaofbothcontex- focusinginparticularonfindingsfromlesionsoftheventralhippocampus tualandtonefear(Anagnostarasetal.,1998).Consider- (VH)anddiscussinghowtheseareproblematicfortheviewwepresented. ingthiskindofevidence,NadelandMoscovitch(1997, AlthoughaspecifichypothesisontheroleoftheVHinfearconditioninghas 2001)haveofferedaviewinwhichthehippocampusis notyetbeenformulated,severalinterestingfindingswerereviewed,empha- permanentlyinvolvedinmemorystorage,challenging sizing,inparticular,theeffectsofcompleteorVHlesionsonbothtone considerableworkonhumanamnesics,includingthat fearconditioningandonremotelyacquiredfear(e.g.,Mumbyetal.,1999; collectedbySquire,whichindicatesatemporaryrolefor Sutherlandetal.,2001).ThesefindingsareincontrasttoDHlesions,in thehippocampusinmemorystorage(Knowltonand whichasevereandselectivedeficitforrecentlyacquiredcontextualfear,but Fanselow,1998;Squireetal.,2001;Murreetal.,2001). notfortoneorremotelyacquiredfear,istypicallyfound(KimandFanselow, IntheNadelandMoscovitchaccount,multiplememory 1992;PhillipsandLeDoux,1992;Marenetal.,1997;Anagnostarasetal., tracescometobeformedovertimeastheresultofre- 1999).Inthisreply,weaddressandexpandonsomeoftheissuesraisedby hearsalorretrieval,whichallowsthisviewtoaccommo- Bastetal.(2001b).Althoughthiscanhelpclarifywhereagreementsliein datetheimmunitytopartialhippocampallesionsthat someoftheempiricalfindings,wefeelthereisnotyetenoughexperimental memorygainsovertime.Althoughthereislittleevidence evidencetoofferaspecificrolefortheVHinfearconditioning,anditisnot tosupportdirectlytheideathatmultiplememorytraces yetclearwhetherthesefindingschallengetheviewsofferedinourreview. areformedwithinthehippocampus,theviewisconsis- However,weagreethat,astheinterfacebetweentheDHandamygdala, tentwiththeempiricaldatafrombothratsandhumans thatretrogradeamnesiaistemporallygradedafterpartial damagetothehippocampus.Inadditionatfirstglance, DOI10.1002/hipo.10071 thefindingthatcompletehippocampuslesionsappearto Publishedonline00Month2002inWileyInterScience(www.interscience. produceatemporallyungradedamnesiaisproblematic wiley.com). fortheSquireconsolidationview(NadelandBohbot, ©2002WILEY-LISS,INC. 562 LETTERS TO THE EDITOR 2001). However, as we stated in our review, the lack of data on pression of eyeblink conditioning. Although aspiration lesions will several fronts is problematic for the Nadel view. In the standard certainly interrupt fibers of passage, perhaps they do not cause as consolidation model, it is argued that memory is transferred from much distal damage or disruption as excitotoxic lesions. Alterna- the hippocampus to the cortex. Indeed, there is an abundance of tively, this may be because the primary site of eyeblink condition- evidence that hippocampus damage produces impairments in re- ing is in the cerebellum, far away from the site of the lesion, rather cent memory while sparing remote memory, and recent evidence than in the amydala, as in fear conditioning. One additional prob- indicates that cortical impairments or damage can produce a re- lem with conclusions drawn from studies using excitotoxins relates verse temporal gradient, impairing remote memory while sparing to the evidence that these toxins produce cell death through oxi- recent memory (Hodges and Graham, 1998; Graham, 1999; dative stress and mitochondrial pathology (e.g., Liang et al., 2000). Frankland et al., 2001; Murre et al., 2001). Moreover, as we stated Cells in the hippocampus probably exhibit massive discharge for a in our review (Anagnostaras et al., 2001), several problems with sustained period of time, perhaps producing catastrophic interfer- studies using complete hippocampus lesions in rats suggest that the ence in other structures that may try to encode this persistent noisy effects may in fact be expected from the Squire consolidation output (e.g., McClelland et al., 1995). This could interfere with model. Specifically, we suggested that kainite-colchicine lesions previously established memories. Moreover, this massive gluta- produce distal damage to the cortex. A study of rats lesioned from mate output could also produce oxidative stress in distal cortical the Sutherland laboratory indicated a 10% reduction in cortical cells, making them more susceptible to cell death later, or reducing volume (Day et al., 1999) and damage to the amygdala has also the efficacy of learning and memory mechanisms, which consider- been shown after kainate injection into the hippocampus (Jarrard ably overlap with the mechanisms involved in mitochondrial and Meldrum, 1990). Indeed, we have recently completed an ex- stress. Indeed, in unpublished work examining ibotenic acid le- tensive study in rats with complete and partial ibotenic acid lesions sions of the hippocampus, we have found considerably more cor- of the hippocampus in a within-subject design very similar to tical damage when histology was done 6 months, as compared with that used by Anagnostaras et al. (1999; for preliminary data, see 4 days after the lesion. Therefore, we suggest that excitoxins may be Anagnostaras et al., 1998). Although the full details of this study less than ideal for the study of retrograde amnesia. Indeed, when will be published elsewhere, we found (1) a severe loss of remote we compared ibotenic acid lesions of the DH with electrolytic and recent context and tone fear after complete hippocampus le- lesions of roughly the same (small) size, electrolytic lesions were sions, similar to partial amygdala lesions; (2) substantial cortical found to produce a highly selective deficit for recent context fear damage after partial (dorsal) or complete ibotenic acid lesions di- (with Ͻ50-day gradient), but excitoxic lesions produced an rected at the hippocampus; (3) damage to the cortex as a better extended gradient (Ͼ100 days) and modest tone deficits (Anag- predictor of remote context and tone memory deficits than hip- nostaras et al., 1998; compare Anagnostaras et al., 1999 with pocampus damage; and (4) severe hyperactivity in rats with com- Maren et al., 1997). These findings will be published in detail plete hippocampus lesions, with a limited ability to produce the elsewhere. Therefore, we suggest that considerable additional work freezing response. Indeed, the mnemonic impairments after com- is necessary to develop effective ways of producing large lesions
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