Experience-dependent inhibitory plasticity is mediated by CCK+ basket cells in the developing dentate gyrus

• Published in: The Journal of neuroscience 2021-05, Vol.41 (21), p.4607-4619
• Main Authors: Feng, Ting, Alicea, Christian, Pham, Vincent, Kirk, Amanda, Pieraut, Simon
• Format: Article
• Language: English
• Subjects: Cannabinoid CB1 receptors; Cholecystokinin; Circuits; Cortex (entorhinal); Dentate gyrus; Early experience; Enrichment; Hippocampal plasticity; Hippocampus; Innervation; Parvalbumin; Photovoltaic cells; Plastic properties; Plasticity; Synapses
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.1207-20.2021

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 pre-weaning 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 (GC) following EE, while 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 DG and shows that cortical inputs to the hippocampus play an instructional role in controlling the refinement of the synaptic connections during the pre-weaning period. Brain plasticity is triggered by experience during postnatal brain development and shapes the maturing neural circuits. In humans, altered experience-dependent plasticity can have long-lasting detrimental effects on circuit function and lead to psychiatric disorders. Yet, the cellular mechanisms governing how early experience fine tune the maturing synaptic network is not fully understood. Here, taking advantage of an enrichment-housing paradigm we unravel a new plasticity mechanism involved in the maintenance of the inhibitory to excitatory balance in the hippocampus. Our findings demonstrate that cortical activity instructs the assembly of the cholecystokinin-expressing (CCK+) basket cell network. Considering the importance of this specific cell-type for learning and memory, experience-dependent remodeling of CCK+ cells may be a critical determinant for establishing appropriate neural networks.