Prefrontal microcircuit underlies contextual learning after hippocampal loss

Moriel Zelikowsky, Stephanie Bissiere, Timothy A Hast, Rebecca Z Bennett, Andrea Abdipranoto, Bryce Vissel, Michael S Fanselow

Research output: Contribution to journalArticleResearchpeer-review

93 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)9938 - 9943
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number24
DOIs
Publication statusPublished - 2013

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