@article{94ef34c300e1413bad87a5e4ca8a224a,
title = "Transient expression of a GABA receptor subunit during early development is critical for inhibitory synapse maturation and function",
abstract = "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 α3-subunit-containing GABAA (GABAAα3) receptors are a key developmental organizer. Before eye opening, GABAAα3 gives way to GABAAα1 at individual BC presynaptic inhibitory synapses. The developmental downregulation of GABAAα3 is independent of GABAAα1 expression. Importantly, lack of early GABAAα3 impairs clustering of GABAAα1 and formation of functional GABAA synapses across mature BC terminals. This impacts the sensitivity of visual responses transmitted through the circuit. Lack of early GABAAα3 also perturbs aggregation of LRRTM4, the organizing protein at GABAergic synapses of rod BC terminals, and their arrangement of output ribbon synapses.",
keywords = "GABA receptor, development, inhibitory circuits, retina, synapse formation",
author = "Raunak Sinha and Grimes, {William N.} and Julie Wallin and Ebbinghaus, {Briana N.} and Kelsey Luu and Timothy Cherry and Fred Rieke and Uwe Rudolph and Wong, {Rachel O.} and Mrinalini Hoon",
note = "Funding Information: This work was supported by NIH grants EY031677 (to M.H.), EY10699 (to R.O.W.), EY026070 (to R.S.), EY028111 (to F.R.), Vision Core Grant EY01730 (to M. Neitz), and Core grant for Vision Research ( P30EY016665 ); the McPherson Eye Research Institute{\textquoteright}s Rebecca Meyer Brown / Retina Research Foundation Professorship (to M.H.); and an unrestricted grant from Research to Prevent Blindness, Inc. to UW Madison Department of Ophthalmology. We thank J.M. Fritschy, R. Enz, S. Haverkamp, and H. W{\"a}ssle for generously providing GABA A and GABA C receptor antibodies; T.J. Siddiqui for generously providing the LRRTM4 antibody; and E. Parker, M. Zhang, and K. Oda for expert technical assistance. Funding Information: This work was supported by NIH grants EY031677 (to M.H.), EY10699 (to R.O.W.), EY026070 (to R.S.), EY028111 (to F.R.), Vision Core Grant EY01730 (to M. Neitz), and Core grant for Vision Research (P30EY016665); the McPherson Eye Research Institute's Rebecca Meyer Brown/Retina Research Foundation Professorship (to M.H.); and an unrestricted grant from Research to Prevent Blindness, Inc. to UW Madison Department of Ophthalmology. We thank J.M. Fritschy, R. Enz, S. Haverkamp, and H. W?ssle for generously providing GABAA and GABAC receptor antibodies; T.J. Siddiqui for generously providing the LRRTM4 antibody; and E. Parker, M. Zhang, and K. Oda for expert technical assistance. M.H. and R.O.W. designed research; R.S. W.N.G. J.W. B.N.E. K.L. T.C. F.R. and M.H. performed research; R.S. W.N.G. J.W. B.N.E. K.L. T.C. and M.H. analyzed data; U.R. contributed new reagents; and R.S. R.O.W. and M.H. wrote the paper. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = oct,
day = "11",
doi = "10.1016/j.cub.2021.07.059",
language = "English (US)",
volume = "31",
pages = "4314--4326.e5",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "19",
}