Dorsal Hippocampus to Infralimbic Cortex Circuit is Essential for the Recall of Extinction Memory

Cereb Cortex. 2021 Feb 5;31(3):1707-1718. doi: 10.1093/cercor/bhaa320.


Posttraumatic stress disorder subjects usually show impaired recall of extinction memory, leading to extinguished fear relapses. However, little is known about the neural mechanisms underlying the impaired recall of extinction memory. We show here that the activity of dorsal hippocampus (dHPC) to infralimbic (IL) cortex circuit is essential for the recall of fear extinction memory in male mice. There were functional neural projections from the dHPC to IL. Using optogenetic manipulations, we observed that silencing the activity of dHPC-IL circuit inhibited recall of extinction memory while stimulating the activity of dHPC-IL circuit facilitated recall of extinction memory. "Impairment of extinction consolidation caused by" conditional deletion of extracellular signal-regulated kinase 2 (ERK2) in the IL prevented the dHPC-IL circuit-mediated recall of extinction memory. Moreover, silencing the dHPC-IL circuit abolished the effect of intra-IL microinjection of ERK enhancer on the recall of extinction memory. Together, we identify a dHPC to IL circuit that mediates the recall of extinction memory, and our data suggest that the dysfunction of dHPC-IL circuit and/or impaired extinction consolidation may contribute to extinguished fear relapses.

Keywords: consolidation of extinction memory; dHPC-IL circuit; extracellular signal-regulated kinase2; post-traumatic stress disorder; recall of extinction memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Classical
  • Extinction, Psychological / physiology*
  • Hippocampus / physiology*
  • Male
  • Memory / physiology*
  • Mice, Inbred C57BL
  • Neural Pathways / physiology*
  • Prefrontal Cortex / physiology*
  • Stress Disorders, Post-Traumatic / physiopathology