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Séminaire impromptu - Shigeo OkabeImaging of synapse dynamics in vitro and in vivo

Abstract :

The development of neural circuits is regulated by a proper balance between synapse formation and elimination. In the early phase of neural circuit development, redundant connections between neurons may exist, but they are thought to be eliminated by the extrinsic instructive signals. In vitro analyses of synapse remodeling require high precision measurements of synapse structure and distribution of functional molecules. We analyzed redistribution of PSD-95, a major postsynaptic scaffold, in excitatory synapses during synaptic plasticity by using the technique of localization microscopy. The data indicated rapid redistribution of PSD-95 in the process of synaptic plasticity and this may be important in structural remodeling of synapses.

Dynamic properties of synapses identified in a reduced preparation of culture system should be reevaluated in tissue environment. We performed in vivo two-photon imaging of single synapses by using GFP-labeled postsynaptic proteins, such as PSD-95-GFP, and revealed rapid turnover of synapses in the mouse neocortex at postnatal 2-3 weeks. Our study indicates that a large fraction of newly generated postsynaptic structures are transient and selective stabilization of specific synapses plays a critical role in establishment of mature neural circuits. The higher rate of synapse turnover in the early postnatal period contrasts with the scarcity of dynamic synapses in the mature cortex. Impairment in this transition of synapse dynamics in the neocortex may underlie the pathophysiology of juvenile-onset neurological disorders. To test this possibility, we are currently studying in vivo dynamics of synapses in mouse models of autism spectrum disorders (ASDs). 

Measurement of synapse remodeling in vitro and in vivo will facilitate our understanding of both physiology and pathology of neuron network functions. 


Shigeo Okabe M.D., Ph.D.
Dept. of Cellular Neurobiology
University of Tokyo