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Publication : Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways.

First Author  Wang Q Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  5540
PubMed ID  36130959 Mgi Jnum  J:328929
Mgi Id  MGI:7340817 Doi  10.1038/s41467-022-33241-9
Citation  Wang Q, et al. (2022) Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways. Nat Commun 13(1):5540
abstractText  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.
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