The molecular signals that regulate activity-dependent synapse refinement in the brain

The formation of appropriate synaptic connections is critical for the proper functioning of the brain. Early in development, neurons form a surplus of immature synapses. To establish efficient, functional neural networks, neurons selectively stabilize active synapses and eliminate less active ones....

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Published in:Current opinion in neurobiology 2023-04, Vol.79, p.102692-102692, Article 102692
Main Authors: Nagappan-Chettiar, Sivapratha, Yasuda, Masahiro, Johnson-Venkatesh, Erin M., Umemori, Hisashi
Format: Article
Language:English
Subjects:
Brain
Elimination signal
Neural activity
Neurons - physiology
Punishment signal
Stabilization signal
Synapse refinement
Synapses - physiology
Synaptic competition
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Summary:The formation of appropriate synaptic connections is critical for the proper functioning of the brain. Early in development, neurons form a surplus of immature synapses. To establish efficient, functional neural networks, neurons selectively stabilize active synapses and eliminate less active ones. This process is known as activity-dependent synapse refinement. Defects in this process have been implicated in neuropsychiatric disorders such as schizophrenia and autism. Here we review the manner and mechanisms by which synapse elimination is regulated through activity-dependent competition. We propose a theoretical framework for the molecular mechanisms of synapse refinement, in which three types of signals regulate the refinement. We then describe the identity of these signals and discuss how multiple molecular signals interact to achieve appropriate synapse refinement in the brain. •Neuronal activity-dependent competition instructs synapse refinement.•The winning synapses send a punishment signal to the losing synapses.•The elimination signal, JAK2, drives the elimination of losing synapses.•Many stabilization signals regulate various aspects of winning synapse maturation.•Neurons and microglia communicate via eat-me and don't-eat-me signals.
ISSN:0959-4388
1873-6882
DOI:10.1016/j.conb.2023.102692