竞争机制介导树突棘的协同修剪与成熟

A Competition-based Mechanism for Coordinated Spine Pruning and Maturation

树突棘是中枢神经系统中绝大多数兴奋性突触的突触后位点。在出生后早期,脑内树突棘大量形成;当个体进入青少年期,脑内树突棘总数逐渐减少,这一过程被称为树突棘修剪,并被认为是神经环路精确化的重要过程。在孤独症谱系障碍、精神分裂症等发育性神经系统疾病中被报道存在树突棘修剪的异常。虽然树突棘修剪的现象已被广泛描述,然而介导该过程的分子机制尚待进一步研究。该研究组近期工作发现,在小鼠触须所对应的感觉皮层,树突棘的修剪与成熟是协同发生的,并且受感觉经验的双向调控。进一步研究发现,神经电活动可以引起相邻树突棘对cadherin/catenin细胞黏附复合物的竞争,导致该复合物的重新分布,并使这两个树突棘的命运产生分化:得到cadherin/catenin复合物的树突棘变得更加成熟而相邻失去这些分子的树突棘变小或被修剪。这一cadherin/catenin复合物依赖的竞争机制为树突棘的协同成熟与修剪提供了特异性,对于理解介导神经环路精确化的机制至关重要。

Dendritic spines are the postsynaptic sites of most excitatory synapses in the central nervous system. In early postnatal life, spines are rapidly formed during the process of spinogenesis. However during the transition through adolescence, a significant amount of spines are actively pruned, a process believed to be critical for neural circuit refinement. Although the phenomenon of spine pruning has been extensively described, and its defects have been implicated in developmental neurological disorders including autism spectrum disorders and schizophrenia, its underlying mechanism remains largely unknown. Our recent study found that in the mouse sensory cortical region receiving tactile inputs from the whiskers, the pruning and maturation of spines were coordinated and bidirectionally regulated by neural activity. We further found the inter-spine competition for cadherin/catenin complexes induced by neural activity mediated the fate differentiation of neighboring spines with the cadherin/catenin-enriched spine becoming more mature at the expense of its neighbor. This cadherin/catenindependent and competition-based model provides specificity for concurrent spine pruning and maturation, and is critical for our understanding of the molecular control of neural circuit refinement.