Role of GABAergic inhibitory interneurons in the emergence of environmental representations in the mouse dentate gyrus

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Representations of spatial environments in hippocampal networks are fundamental building blocks to the narrative of our lives. They allow us to rapidly and flexibly respond to changes within our environment. Although hippocampal principal cell (PC) assemblies have been shown to encode unique experienced environments and their re-activation is thought to reinstate the associated memory, the role of GABAergic inhibitory interneurons (INs) in the formation and stabilization of spatial representations is largely unknown. In the proposed project, (1) we aim to address this fundamental question by recording the activity of hippocampal PC and IN populations at high spatial and temporal resolution using 2-photon calcium imaging in head-fixed mice navigating through virtual environments and learn to obtain goal-oriented rewards. (2) We aim to modulate IN activity using pharmaco- and/or optogenetic tools to examine their influence on spatial representation by PC assemblies. (3) We will develop based on our established computational network models, theories on circuit mechanisms underlying the spatial and contextual representation in the dentate gyrus (DG), as the input gate of the hippocampus. A large body of work has previously identified a high diversity of morphologically, physiologically and neurochemically distinct hippocampal IN types. We will therefore focus the proposed project on examining the role of parvalbumin (PV)-expressing perisomatic-inhibitory and somatostatin (SOM)-positive distal dendrite-inhibiting INs (PVIs, SOMIs, respectively) in the DG, which is functionally vital for spatial and contextual representation in the hippocampus. Thus, our major goal is to examine how IN types influence the activity dynamics of individual PCs and PC assemblies representing a given environment in the DG. This project will contribute to our understanding on the role of IN types in the representation and encoding of environmental information and the differentiation between environments.