Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding.
The prefrontal cortex (PFC) is crucial for accurate memory performance when prior knowledge interferes with new learning, but the mechanisms that minimize proactive interference are unknown. To investigate these, we assessed the influence of medial PFC (mPFC) activity on spatial learning and hippocampal coding in a plus maze task that requires both structures. mPFC inactivation did not impair spatial learning or retrieval per se, but impaired the ability to follow changing spatial rules. mPFC and CA1 ensembles recorded simultaneously predicted goal choices and tracked changing rules; inactivating mPFC attenuated CA1 prospective coding. mPFC activity modified CA1 codes during learning, which in turn predicted how quickly rats adapted to subsequent rule changes. The results suggest that task rules signaled by the mPFC become incorporated into hippocampal representations and support prospective coding. By this mechanism, mPFC activity prevents interference by "teaching" the hippocampus to retrieve distinct representations of similar circumstances.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Kevin G
KG
Guise
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: matthew.shapiro@mssm.edu.
Matthew L
ML
Shapiro
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology; D007858:Learning / Q000187:drug effects / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology
D058785:GABA-A Receptor Agonists; D009118:Muscimol
CA1; hippocampus; learning; memory; neuronal representation; prefrontal cortex; proactive interference; recall; retrieval