Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning

Abstract

Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP⁺), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP⁺ INs and computational modeling further showed that VIP⁺ disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning. VIDEO ABSTRACT.

Keywords: VIP; disinhibition; hippocampus; inhibition; place cell; reward; spatial learning; two-photon.