DISTINCT DEVELOPMENTAL PROGRAMS GOVERN SYNAPTIC DISTRIBUTION AND INTEGRATION IN PV AND SST INTERNEURONS

Balanced excitation–inhibition interactions are essential for cortical computation. In the neocortex, inhibition is mediated by GABAergic interneurons (INs), whose activity is shaped by excitatory synaptic inputs distributed along their dendrites. While dendritic integration is well characterized in excitatory neurons, mechanisms by which interneuron dendrites integrate synaptic inputs and generate cell-type-specific circuit functions remain poorly understood. We previously showed that, in mouse primary visual cortex, excitatory synapses are organized in cell-type-specific manner along dendrites of parvalbumin (PV) and somatostatin (SST) interneurons, the principal inhibitory classes regulating pyramidal neuron activity. Synapse density is uniform along SST-IN dendrites, whereas PV-INs exhibit a strong proximal bias, with density decreasing with distance from the soma. This asymmetric synaptic architecture correlates with distinct NMDA receptor–dependent dendritic integration properties (Morabito et al., Neuron, 2025), but how it is established during development remains unknown. To define these mechanisms, we investigated the developmental emergence of synaptic organization and dendritic integration in PV- and SST-INs. We combined electrophysiological recordings with two-photon calcium imaging and morpho-functional analyses of excitatory synapse distribution across postnatal development. We find that PV-INs preserve synaptic architecture while undergoing receptor-level changes modulating dendritic integration. In contrast, SST-INs exhibit extensive postnatal remodeling of synaptic distribution, characterized by progressive addition of excitatory synapses, particularly in distal dendritic compartments, after eye opening. Genetic disruption of NMDA receptor signaling selectively impairs this SST-IN remodeling. Together, these findings reveal interneuron-specific developmental programs that link NMDA receptor signaling to the establishment of dendritic synaptic architecture and integration in cortical inhibitory circuits.