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Imaging Synapse Formation and Remodeling In Vitro and In Vivo

S. Okabe

Published 2019 in Make Life Visible

ABSTRACT

Live-cell imaging technique contributes to the progress of modern life science, especially in the field of neurobiology. Molecular mechanism of regulation in synapse formation, maturation, elimination, and remodeling can be effectively studied by imaging of living neurons, neural tissues isolated in vitro, and neural circuits functioning in vivo. In vitro imaging of synapse development by expression of fluorescent protein-tagged synaptic molecules in single neurons revealed rapid recruitment of synaptic molecules and structural differentiation that can be completed within several hours. In vivo two-photon excitation microscopy enabled direct measurement of synapse turnover in living animals. Although more than 90% of spine synapses are stabilized for more than months in the adult mouse neocortex, neural circuits were found to be under active rewiring in the early postnatal period, with the rate of synapse turnover comparable to that in dissociated cultures. Subsequent stabilization of spine synapse dynamics takes place at postnatal 3–4 weeks. Because multiple mouse models of autism spectrum disorders show identical phenotypes in upregulation of spine turnover at postnatal 3 weeks, prolonged functional impairment in the adult neocortex may be derived from increased misconnection of developing cortical neurons through accelerated turnover. Imaging of synapse turnover in vitro and in vivo is an indispensable experimental approach to understanding the construction principles of neural circuits in both physiological and pathological conditions.

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