GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex

During neonatal development, sensory cortices generate spontaneous activity patterns shaped by both sensory experience and intrinsic influences. How these patterns contribute to the assembly of neuronal circuits is not clearly understood. Using longitudinal in vivo calcium imaging in un-anesthetized mouse pups, we show that spatially segregated functional assemblies composed of interneurons and pyramidal cells are prominent in the somatosensory cortex by postnatal day (P) 7. Both reduction of GABA release and synaptic inputs onto pyramidal cells erode the emergence of functional topography, leading to increased network synchrony. This aberrant pattern effectively blocks interneuron apoptosis, causing increased survival of parvalbumin and somatostatin interneurons. Furthermore, the effect of GABA on apoptosis is mediated by inputs from medial ganglionic eminence (MGE)-derived but not caudal ganglionic eminence (CGE)-derived interneurons. These findings indicate that immature MGE interneurons are fundamental for shaping GABA-driven activity patterns that balance the number of interneurons integrating into maturing cortical networks. [Display omitted] •GABA limits MGE-cIN participation in synchronous network events during development•Synaptic GABA regulates the emergence of interneuron-pyramidal cell assemblies•GABAergic restriction of pyramidal cell activity is required for MGE-cIN apoptosis•GABAAγ2-containing GABAA receptors are essential for interneuron apoptosis Duan, Che, Chu et al. use genetic tools and in vivo imaging to show that cortical GABAergic signaling restricts functional assemblies and enables developmental apoptosis of MGE interneurons, balancing the number of interneurons integrating into maturing cortical networks.