Synaptic assembly of the brain in the absence of neurotransmitter secretion

Brain function requires precisely orchestrated connectivity between neurons . Establishment of these connections is believed to require signals secrete d from outgrowing axons, followed by synapse formation between selected neu rons. Deletion of a single protein, Munc18-1, in mice Leads to a complete L oss of neurotransmitter secretion from synaptic vesicles throughout develop ment. However, this does not prevent normal brain assembly, including forma tion of Layered structures, fiber pathways, and morphologically defined syn apses. After assembly is completed, neurons undergo apoptosis, leading to w idespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter sec retion probably functions to validate already established synaptic connecti ons.