Sex-specific frontal cortical circuit mechanisms mediating fear extinction
Overview
- The Jackson Laboratory, Bar Harbor, ME, 04690 United States
- Janelia Research Campus, Ashburn, VA, 21047 United States
- IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, China, 100084
Abstract
Strong evidence suggests synaptic plasticity is the critical cellular mechanism underlying learning and memory. Although the forms of synaptic plasticity used by different circuits vary, a widespread presumption is that the male and female brain has evolved to use the same form of plasticity within the same circuits during learning. We used complimentary approaches to determine how synaptic plasticity within the mouse frontal cortex supports extinction of associative memories. Here, we show that both male and female mice have similar ensemble dynamics in excitatory infralimbic cortical neurons during learning. However, activity in amygdala-projecting neurons was required for extinction memories only in male mice. Likewise, only male mice showed evidence for structural synaptic remodeling and clustering of dendritic spines on infralimbic-amygdala projection neurons. Projection-specific deletion of the glutamate receptor subunit GRIN2B blocked synaptic plasticity and impaired extinction memory in male but not female mice. These distinct mechanisms could be leveraged for precise therapies for mental health conditions relative to the present one-size-fits-all approach.
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Recorded: type, language, journal, pages, dates, 8 authors, 1 funder, 63 references.
Cite
This paper
Graham, K., Pomeroy-Tuck, J., O’Brien, G. K., Kent-Webber, L., Drillen, A. L., Coddington, L., Zhao, X., & Bloss, E. B. (2026). Sex-specific frontal cortical circuit mechanisms mediating fear extinction. bioRxiv : the preprint server for biology, 2026.04.10.717763.
BibTeX
@article{graham2026sex,
author = {Graham, Kourtney and Pomeroy-Tuck, Justice and O’Brien, Grace K. and Kent-Webber, Lacey and Drillen, Anna L. and Coddington, Luke and Zhao, Xinyu and Bloss, Erik B.},
title = {{Sex-specific frontal cortical circuit mechanisms mediating fear extinction}},
journal = {bioRxiv : the preprint server for biology},
year = {2026},
month = may,
pages = {2026.04.10.717763},
publisher = {bioRxiv},
issn = {2692-8205},
pmcid = {PMC13228363}
}
RIS
TY - JOUR
AU - Graham, Kourtney
AU - Pomeroy-Tuck, Justice
AU - O’Brien, Grace K.
AU - Kent-Webber, Lacey
AU - Drillen, Anna L.
AU - Coddington, Luke
AU - Zhao, Xinyu
AU - Bloss, Erik B.
TI - Sex-specific frontal cortical circuit mechanisms mediating fear extinction
T2 - bioRxiv : the preprint server for biology
J2 - bioRxiv
PY - 2026
DA - 2026/
SP - 2026.04.10.717763
SN - 2692-8205
PB - bioRxiv
LA - en
ER -
CSL-JSON
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