Synapse formation and remodeling visualized in physiological and pathological states

Abstract

The development of neuronal circuits in vivo depends on precise regulation of synapse formation, elimination, and remodeling. In vivo two-photon imaging confirmed the presence of two phases of synapse dynamics in the postnatal mouse cortex. In the first phase (until postnatal 20 days), synapse turnover is maintained to be high, while in the second phase (after three weeks postnatal), synapse dynamics are highly suppressed, leading to the maturation of the cortical neural network. The transition in synapse dynamics may underlie the pathophysiology of neurodevelopmental disorders and psychiatric diseases, but their precise mechanisms have not yet been clarified. Our laboratory has focused on (1) the diverse mechanisms in neural circuits and synapse formation, (2) the structure-function relationship in dynamic synaptic changes, and (3) the relationship between brain diseases and synaptic dysfunction. In particular, we have recently developed new tools for studying neural circuits, such as quantitative methods for analyzing the nano-structure of spine synapses and methods for measuring the molecular dynamics inside spines. Furthermore, we are applying these tools to the study of brain pathology. In this talk, I will introduce these researches and discuss the validity and prospects of understanding the pathogenesis of psychiatric disorders as synaptic dysfunction.