Fluorescence imaging of synapse dynamics in normal circuit maturation and in developmental disorders

Abstract

One of the most fundamental questions in neurobiology is how proper synaptic connections are established in the developing brain. Live-cell imaging of the synaptic structure and functional molecules can reveal the time course of synapse formation, molecular dynamics, and functional maturation. Using postsynaptic scaffolding proteins as a marker of synapse development, fluorescence time-lapse imaging revealed rapid formation of individual synapses that occurred within hours and their remodeling in culture preparations. In vivo two-photon excitation microscopy development enabled us to directly measure synapse turnover in living animals. In vivo synapse dynamics were suppressed in the adult rodent brain, but were maintained at a high level during the early postnatal period. This transition in synapse dynamics is biologically important and can be linked to the pathology of juvenile-onset psychiatric diseases. Indeed, the upregulation of synapse dynamics was observed in multiple mouse models of autism spectrum disorders. Fluorescence imaging of synapses provides new information regarding the physiology and pathology of neural circuit construction.