Kavli Affiliate: Vikaas Sohal
| Authors: Shana E Silverstein, Thomas T Clarity, Meena S Deshpande, Erik Vaughan, Shoshana Novik, Hector E Yarur, Shiliang Zhang, Valerie S Tsai, Rong Ye, Rachel M Mikofsky, Madeline Hsiang, Avery Bauman, Gabriel Loewinger, Francisco Pereira, Marisela Morales, Vikaas S Sohal, Hugo Tejeda, Joshua A Gordon and David A Kupferschmidt
| Summary:
Long-range projections from ventral hippocampus (vHPC) to medial prefrontal cortex (mPFC) support cognitive functions including spatial working memory (SWM). vHPC input targets multiple prefrontal interneuron classes, yet how hippocampal input recruits these populations in vivo, whether this recruitment is plastic, and how such plasticity influences cognition remain unknown. Here, we combined optical stimulation of mouse vHPC inputs with calcium recordings from discrete mPFC interneuron populations, revealing persistent activity-induced reweighting of hippocampal recruitment across prefrontal inhibitory microcircuits. Ex vivo electrophysiology and computational modeling implicated weakened monosynaptic hippocampal drive onto vasoactive intestinal polypeptide (VIP)-expressing interneurons in this circuit reconfiguration. Prior vHPC input stimulation and the schizophrenia-associated Df(16)A+/– mutation, which also yielded reduced hippocampal input onto VIP interneurons, produced convergent alterations in task-related VIP interneuron activity associated with poorer SWM task learning. These findings implicate hippocampal input to VIP interneurons as a key locus of plasticity capable of reconfiguring inhibitory microcircuit activity linked to impaired working memory task learning.