Experience-Dependent Inhibitory Plasticity Is Mediated by CCK+ Basket Cells in the Developing Dentate Gyrus.

Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm during the preweaning period in mice of either sex, we assessed the circuit plasticity of inhibitory cell types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GCs) following EE, whereas another pivotal inhibitory cell type, parvalbumin (PV)-expressing cells, did not show changes. Using electrophysiological analysis and the use of cannabinoid receptor 1 (CB1R) agonist WIN 55 212-2, we demonstrate that the change in somatic inhibition from CCK+ neurons increases CB1R-mediated inhibition in the circuit. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we further demonstrate that the activity of the projections from the EC mediates the developmental assembly of CCK+ basket cell network. Altogether, our study places the experience-dependent remodeling of CCK+ basket cell innervation as a central process to adjust inhibition in the dentate gyrus and shows that cortical inputs to the hippocampus play an instructional role in controlling the refinement of the synaptic connections during the preweaning period.