title: Prefrontal microcircuit underlies contextual learning after hippocampal loss.
abstract: Specific brain circuits have been classically linked to dedicated functions. However, compensation following brain damage suggests that these circuits are capable of dynamic adaptation. Such compensation is exemplified by Pavlovian fear conditioning following damage to the dorsal hippocampus (DH). Although the DH normally underlies contextual fear and fear renewal after extinction, both can be learned in the absence of the DH, although the mechanisms and nature of this compensation are currently unknown. Here, we report that recruitment of alternate structures, specifically the infralimbic and prelimbic prefrontal cortices, is required for compensation following damage to the hippocampus. Disconnection of these cortices in DH-compromised animals and immediate early gene induction profiles for amygdala-projecting prefrontal cells revealed that communication and dynamic rebalancing within this prefrontal microcircuit is critical. Additionally, the infralimbic cortex normally plays a role in limiting generalization of contextual fear. These discoveries reveal that plasticity through recruitment of alternate circuits allows the brain to compensate following damage, offering promise for targeted treatment of memory disorders.
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Moriel
authors.initials: M
authors.lastname: Zelikowsky
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bissiere
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hast
authors.forename: Rebecca Z
authors.initials: RZ
authors.lastname: Bennett
authors.forename: Andrea
authors.initials: A
authors.lastname: Abdipranoto
authors.forename: Bryce
authors.initials: B
authors.lastname: Vissel
authors.forename: Michael S
authors.initials: MS
authors.lastname: Fanselow
mesh_terms: D000648:Amnesia, Retrograde / Q000503:physiopathology; D000679:Amygdala / Q000378:metabolism / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology*; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020318:Rats, Long-Evans
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: amnesia; anxiety; medial prefrontal cortex; recovery of function