During development, neural circuits are remodeled — some synapses are eliminated and others are strengthened — to produce a mature, functional nervous system. Circuit refinement occurs during “critical periods” when genetic programs intersect with neural activity, but the molecular components that link genetics and activity are poorly understood.
Tyne Miller-Fleming, a Neuroscience graduate student in the laboratory of David Miller, Ph.D., led a research team that explored the mechanism of synaptic remodeling in the nematode worm C. elegans. The investigators focused on a well-defined circuit in which GABA motor neuron synapses are eliminated and then relocated to new positions.
The researchers show that UNC-8, a member of a family of sodium channel proteins with human homologs, is genetically regulated to trigger synapse removal in GABA neurons. This effect requires calcium, which is elevated in active GABA neurons.
The findings, reported in the journal eLife, suggest that UNC-8 serves as a link between genetic and activity-dependent pathways that function together to regulate the elimination of GABA synapses in remodeling neurons.
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