Marek Roger, Jin Jingji, Goode Travis D, Giustino Thomas F, Wang Qian, Acca Gillian M, Holehonnur Roopashri, Ploski Jonathan E, Fitzgerald Paul J, Lynagh Timothy, Lynch Joseph W, Maren Stephen, Sah Pankaj
Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
Department of Psychological and Brain Sciences and the Institute for Neuroscience, Texas A&M University, College Station, TX, USA.
Nat Neurosci. 2018 Mar;21(3):384-392. doi: 10.1038/s41593-018-0073-9. Epub 2018 Feb 5.
The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together, our findings describe a previously unknown circuit mechanism for the contextual control of fear, and indicate that vHPC-mediated inhibition of IL is an essential neural substrate for fear relapse.
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