Activity-Dependent Synapse Refinement: From Mechanisms to Molecules

Author:

Nagappan-Chettiar Sivapratha1ORCID,Burbridge Timothy J.1,Umemori Hisashi1ORCID

Affiliation:

1. Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

Abstract

The refinement of immature neuronal networks into efficient mature ones is critical to nervous system development and function. This process of synapse refinement is driven by the neuronal activity–dependent competition of converging synaptic inputs, resulting in the elimination of weak inputs and the stabilization of strong ones. Neuronal activity, whether in the form of spontaneous activity or experience-evoked activity, is known to drive synapse refinement in numerous brain regions. More recent studies are now revealing the manner and mechanisms by which neuronal activity is detected and converted into molecular signals that appropriately regulate the elimination of weaker synapses and stabilization of stronger ones. Here, we highlight how spontaneous activity and evoked activity instruct neuronal activity–dependent competition during synapse refinement. We then focus on how neuronal activity is transformed into the molecular cues that determine and execute synapse refinement. A comprehensive understanding of the mechanisms underlying synapse refinement can lead to novel therapeutic strategies in neuropsychiatric diseases characterized by aberrant synaptic function.

Funder

National Institute of Neurological Disorders and Stroke

Goldenson Postdoctoral Fellowship

Edward R. and Anne G. Lefler Postdoctoral Fellowship

National Institute of Mental Health

Publisher

SAGE Publications

Subject

Neurology (clinical),General Neuroscience

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