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Publication : Transient expression of a GABA receptor subunit during early development is critical for inhibitory synapse maturation and function.

First Author  Sinha R Year  2021
Journal  Curr Biol Volume  31
Issue  19 Pages  4314-4326.e5
PubMed ID  34433078 Mgi Jnum  J:314267
Mgi Id  MGI:6810653 Doi  10.1016/j.cub.2021.07.059
Citation  Sinha R, et al. (2021) Transient expression of a GABA receptor subunit during early development is critical for inhibitory synapse maturation and function. Curr Biol 31(19):4314-4326.e5
abstractText  Developing neural circuits, including GABAergic circuits, switch receptor types. But the role of early GABA receptor expression for establishment of functional inhibitory circuits remains unclear. Tracking the development of GABAergic synapses across axon terminals of retinal bipolar cells (BCs), we uncovered a crucial role of early GABAA receptor expression for the formation and function of presynaptic inhibitory synapses. Specifically, early alpha3-subunit-containing GABAA (GABAAalpha3) receptors are a key developmental organizer. Before eye opening, GABAAalpha3 gives way to GABAAalpha1 at individual BC presynaptic inhibitory synapses. The developmental downregulation of GABAAalpha3 is independent of GABAAalpha1 expression. Importantly, lack of early GABAAalpha3 impairs clustering of GABAAalpha1 and formation of functional GABAA synapses across mature BC terminals. This impacts the sensitivity of visual responses transmitted through the circuit. Lack of early GABAAalpha3 also perturbs aggregation of LRRTM4, the organizing protein at GABAergic synapses of rod BC terminals, and their arrangement of output ribbon synapses.
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