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Publication : A Disinhibitory Microcircuit Mediates Conditioned Social Fear in the Prefrontal Cortex.

First Author  Xu H Year  2019
Journal  Neuron Volume  102
Issue  3 Pages  668-682.e5
PubMed ID  30898376 Mgi Jnum  J:358675
Mgi Id  MGI:6314066 Doi  10.1016/j.neuron.2019.02.026
Citation  Xu H, et al. (2019) A Disinhibitory Microcircuit Mediates Conditioned Social Fear in the Prefrontal Cortex. Neuron 102(3):668-682.e5
abstractText  Fear behavior is under tight control of the prefrontal cortex, but the underlying microcircuit mechanism remains elusive. In particular, it is unclear how distinct subtypes of inhibitory interneurons (INs) within prefrontal cortex interact and contribute to fear expression. We employed a social fear conditioning paradigm and induced robust social fear in mice. We found that social fear is characterized by activation of dorsal medial prefrontal cortex (dmPFC) and is largely diminished by dmPFC inactivation. With a combination of in vivo electrophysiological recordings and fiber photometry together with cell-type-specific pharmacogenetics, we further demonstrated that somatostatin (SST) INs suppressed parvalbumin (PV) INs and disinhibited pyramidal cells and consequently enhanced dmPFC output to mediate social fear responses. These results reveal a previously unknown disinhibitory microcircuit in prefrontal cortex through interactions between IN subtypes and suggest that SST INs-mediated disinhibition represents an important circuit mechanism in gating social fear behavior.
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