Neurosci. 2018 Feb 5. doi: 10.1038/s41593-018-0073-9.
Hippocampus-driven feed-forward inhibition of the prefrontal
cortex mediates relapse of extinguished fear.
R1, Jin J2, Goode TD2, Giustino TF2, Wang Q3, Acca GM2, Holehonnur R4, Ploski JE4,
Fitzgerald PJ2, Lynagh T5, Lynch JW1, Maren S6, Sah P7.
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.