Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development

兴奋性和抑制性突触表现出紧密的亚细胞相关性,但随着发育逐渐减弱

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作者:Sally Horton, Vincenzo Mastrolia, Rachel E Jackson, Sarah Kemlo, Pedro M Pereira Machado, Maria Alejandra Carbajal, Robert Hindges, Roland A Fleck, Paulo Aguiar, Guilherme Neves, Juan Burrone

Abstract

Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (<20 μm) and, surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilizing scaffold to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.

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