Insular Cortical Circuits as an Executive Gateway to Decipher Threat or Extinction Memory via Distinct Subcortical Pathways

Authors

Qi Wang
Jia-Jie Zhu
Lizhao Wang
Yan-Peng Kan
Yan-Mei Liu
Yan-Jiao Wu
Xue Gu
Xin Yi
Ze-Jie Lin
Qin Wang
Jian-Fei Lu
Qin Jiang
Ying Li
Ming-Gang Liu
Nan-Jie Xu
Michael X Zhu
Lu-Yang Wang
Siyu Zhang
Wei-Guang Li
Tian-Le Xu

Publication Date

9-21-2022

Journal

Nature Communications

Abstract

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC.

Keywords

Animals, Extinction, Psychological, Fear, Male, Mice, Neurons, Nucleus Accumbens, Prefrontal Cortex

DOI

10.1038/s41467-022-33241-9

PMID

36130959

PMCID

PMC9492683

PubMedCentral® Posted Date

9-21-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes