研究セミナー Activity-regulated transcription program underlying homeostatic synaptic plasticity

Homeostatic plasticity represents the fundamental cellular mechanism by which neurons and neural networks stably maintain their activity within a functional dynamic range in the face of perturbing force or activity. Global synaptic scaling is a form of homeostatic synaptic plasticity that adjusts synaptic strengths bi-directionally to stabilize average neuronal firing rates in the cases of altered neural activity. It occurs cell-autonomously over a chronic time scale and requires nuclear transcription. However the nature of the transcription program and associated signaling pathways that underlie synaptic scaling have not been well defined. We have been interested in understanding the nature of the transcription program that specifically operates to promote the cell-wide response for up-regulating synaptic strength when neuronal activity is chronically suppressed. We have applied various genome-wide approaches to systematically identify and characterize the molecular nature of this transcription program. We have also investigated how calcium signaling specifies gene induction and whether the genes that are induced by chronic activity suppression are functionally important for mediating synaptic scaling.