Role of Efficient Neurotransmitter Release in Barrel Map Development

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Abstract
Cortical maps are remarkably precise, with organized arrays of thalamocortical afferents (TCAs) that project into distinct neuronal modules. Here, we present evidence for the involvement of efficient neurotransmitter release in mouse cortical barrel map development usingbarrellessmice, a loss-of-function mutant of calcium/calmodulin-activated adenylyl cyclase I (AC1), and mice with a mutation in Rab3-interacting molecule 1α (RIM1α), an active zone protein that regulates neurotransmitter release. We demonstrate that release efficacy is substantially decreased inbarrellessTCAs. We identify RIMs as important phosphorylation targets for AC1 in the presynaptic terminal. We further show that RIM1α mutant mice have reduced TCA neurotransmitter release efficacy and barrel map deficits, although not as severe as those found inbarrellessmice. This supports the role of RIM proteins in mediating, in part, AC1 signaling in barrel map development. Finally, we present a model to show how inadequacies in presynaptic function can interfere with activity-dependent processes in neuronal circuit formation. These results demonstrate how efficient synaptic transmission mediated by AC1 function contributes to the development of cortical barrel maps.