title: Higher-order conditioning is impaired by hippocampal lesions.
abstract: Behavior in the real world is rarely motivated by primary conditioned stimuli that have been directly associated with potent unconditioned reinforcers. Instead, motivation and choice behavior are driven by complex chains of higher-order associations that are only indirectly linked to intrinsic reward and often exert their influence outside awareness. Second-order conditioning (SOC) [1] is a basic associative-learning mechanism whereby stimuli acquire motivational salience by proxy, in the absence of primary incentives [2, 3]. Memory-systems theories consider first-order conditioning (FOC) and SOC to be prime examples of hippocampal-independent nondeclarative memory [4, 5]. Accordingly, neurobiological models of SOC focus almost exclusively on nondeclarative neural systems that support motivational salience and reward value. Transfer of value from a conditioned stimulus to a neutral stimulus is thought to require the basolateral amygdala [6, 7] and the ventral striatum [2, 3], but not the hippocampus. We developed a new paradigm to measure appetitive SOC of tones in rats. Hippocampal lesions severely impaired both acquisition and expression of SOC despite normal FOC. Unlike controls, rats with hippocampal lesions could not discriminate between positive and negative secondary conditioned tones, although they exhibited general familiarity with previously presented tones compared with new tones. Importantly, normal rats' behavior, in contrast to that of hippocampal groups, also revealed different confidence levels as indexed by effort, a central characteristic of hippocampal relational memory. The results indicate, contrary to current systems models, that representations of intrinsic relationships between reward value, stimulus identity, and motivation require hippocampal mediation when these relationships are of a higher order.
authors.affiliation: Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada; Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario M5S 3G3, Canada. Electronic address: agilboa@research.baycrest.org.
authors.forename: Asaf
authors.initials: A
authors.lastname: Gilboa
authors.affiliation: Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Sekeres
authors.affiliation: Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada; Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario M5S 3G3, Canada.
authors.forename: Morris
authors.initials: M
authors.lastname: Moscovitch
authors.affiliation: Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada; Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario M5S 3G3, Canada; Department of Psychology, Trent University, 1600 West Bank Drive, Peterborough, Ontario K9J 7B8, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Winocur
mesh_terms: D000818:Animals; D001307:Auditory Perception; D003214:Conditioning, Classical; D006624:Hippocampus / Q000293:injuries / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D008568:Memory; D009042:Motivation; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward