Higher-order conditioning is impaired by hippocampal lesions.

作者: Asaf Gilboa , Melanie Sekeres , Morris Moscovitch , Gordon Winocur

DOI: 10.1016/J.CUB.2014.07.078

关键词: NeuroscienceNeutral stimulusHippocampal formationReward valueSecond-order conditioningBasolateral amygdalaVentral striatumBiologyStimulus (physiology)Conditioning

摘要: Department of Psychology, Trent University, 1600 West BankDrive, Peterborough, Ontario K9J 7B8, CanadaSummaryBehavior in the real world is rarely motivated by primaryconditioned stimuli that have been directly associated withpotent unconditioned reinforcers. Instead, motivation andchoice behavior are driven complex chains higher-or-der associations only indirectly linked to intrinsicreward and often exert their influence outside awareness.Second-order conditioning (SOC) [1] a basic associative-learning mechanism whereby acquire motivationalsalience proxy, absence primary incentives [2,3]. Memory-systems theories consider first-order condition-ing(FOC)andSOCtobeprimeexamplesofhippocampal-in-dependent nondeclarative memory [4, 5]. Accordingly,neurobiological models SOC focus almost exclusivelyon neural systems support reward value. Transfer value from condi-tioned stimulus neutral thought requirethe basolateral amygdala [6, 7] ventral striatum[2, 3], but not hippocampus. We developed new para-digm measure appetitive tones rats. Hippocam-pal lesions severely impaired both acquisition expres-sion despite normal FOC. Unlike controls, rats withhippocampal could discriminate between posi-tive negative secondary conditioned tones, althoughthey exhibited general familiarity with previously presentedtones compared tones. Importantly, rats’behavior, contrast hippocampal groups, alsorevealed different confidence levels as indexed effort,a central characteristic relational memory.The results indicate, contrary current models,that representations intrinsic relationships betweenreward value, identity, requirehippocampal mediation when these ahigher order.Results DiscussionWe paradigm test hedonic second-orderconditioning using auditory stim-uli(seeTableS4availableonline)thatpredictedwhetherwaterwould be available neighboring chamber. The paradigmalso allowed insight into rats’ ‘‘confidence’’ makingresponse choices [8]. In this task (see Figure 1, ExperimentalProcedures, Supplemental Experimental Procedures),rats acquired (FOC) two-tone discrimination procedure signifying availability ofwater opposite side positive(CS+)andnegative(CS2)conditionedstimuliwerethenpairedwith (SO+, SO2), followed testing FOCand SOC. three experiments, we tested eitherretrograde (experiments 1a 1b) or anterograde (experi-ment 2) following surgical intervention byusing eithermultiple (experiment 1a) single 1b sec-ondary Following Fortin et al. [8], multiple SOs wereused experiment allow use barriers differentheights challenge approach reward, indexing therats’ response choice. Theuse also us certain ratsdeveloped genuine rather than demonstrate generaliza-tion CS SO.On average, destroyed about 73% hippo-campus, including 84% dorsal 55% hippocam-pus (Figure 2; S1; Table Results).Experiment 1aAs evident 3A, sham-sur-gerycontrolgroupsequallyandsuccessfullydiscriminatedthepositive (rewarded) (nonrewarded) during FOC (F[1,20] = 257.44, p < 0.001;h

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