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

GABAergic 对网络动力学的限制调节发育皮层中的中间神经元存活

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作者:Zhe Ran S Duan, Alicia Che, Philip Chu, Laura Modol, Yannick Bollmann, Rachel Babij, Robert N Fetcho, Takumi Otsuka, Marc V Fuccillo, Conor Liston, David J Pisapia, Rosa Cossart, Natalia V De Marco García

Abstract

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.

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