生命科学联合中心学术报告

题目：Winner take all: molecular mechanism underlying activity-dependent neural circuit refinement

报告人：Xiang YU

Investigator and head of Laboratory of Dendrite Development and Neural Circuit Formation,

Institute of Neuroscience, Chinese Academy of Sciences

时间：2015-11-17（周二），13:00-14:00pm

地点：英国威廉希尔公司邓祐才报告厅

联系人：张岱  北大-清华生命科学联合中心

Dendritic spines are postsynaptic compartments of excitatory synapses that undergo dynamic changes during development, including rapid spinogenesis in early postnatal life and significant pruning during adolescence. Spine pruning defects have been implicated in developmental neurological disorders such as autism, yet much remains to be uncovered regarding its molecular mechanism. Here, we showed that spine pruning and maturation in the mouse somatosensory cortex are coordinated via the cadherin/catenin cell adhesion complex and bidrectionally regulated by sensory experience, i.e. accelerated by environmental enrichment (EE) and blocked by whisker deprivation. We further demonstrated using live imaging in cultured neurons that locally enhancing cadherin/catenin-dependent adhesion or photo-stimulating a contacting channelrhodopsin-expressing axon stabilized the manipulated spine and eliminated its neighbors, an effect requiring cadherin/catenin-dependent adhesion and depending on the inter-spine distance. Importantly, when we overexpressed β-catenin in a subset of presynaptic axons in the mouse somatosensory cortex, thus differentiating the level of cadherin/catenin-dependent adhesion between neighboring spines of the same postsynaptic neuron in vivo, we observed enhanced survival of the spine contacting the β-catenin overexpressing axon, at the expense of its β-catenin deprived neighbor. Thus, we demonstrated, both in vitro and in vivo, that inter-spine competition for cadherin/catenin complexes biased spine fate. Finally, both EE-induced acceleration of spine pruning and spine maturation were abolished in the absence of endogenous β-catenin. Together, these results suggest that activity-induced inter-spine competition for β-catenin provides specificity for concurrent spine maturation and elimination, and thus is critical for the molecular control of spine pruning during neural circuit refinement.

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