@article{57de7e9bf15546c4bc7b2f25d09220fd,
title = "Apoptosis Regulates ipRGC Spacing Necessary for Rods and Cones to Drive Circadian Photoentrainment",
abstract = "The retina consists of ordered arrays of individual types of neurons for processing vision. Here, we show that such order is necessary for intrinsically photosensitive retinal ganglion cells (ipRGCs) to function as irradiance detectors. We found that during development, ipRGCs undergo proximity-dependent Bax-mediated apoptosis. Bax mutant mice exhibit disrupted ipRGC spacing and dendritic stratification with an increase in abnormally localized synapses. ipRGCs are the sole conduit for light input to circadian photoentrainment, and either their melanopsin-based photosensitivity or ability to relay rod/cone input is sufficient for circadian photoentrainment. Remarkably, the disrupted ipRGC spacing does not affect melanopsin-based circadian photoentrainment but severely impairs rod/cone-driven photoentrainment. We demonstrate reduced rod/cone-driven cFos activation and electrophysiological responses in ipRGCs, suggesting that impaired synaptic input to ipRGCs underlies the photoentrainment deficits. Thus, for irradiance detection, developmental apoptosis is necessary for the spacing and connectivity of ipRGCs that underlie their functioning within a neural network",
author = "Chen, {Shih Kuo} and Chew, {Kylie S.} and McNeill, {David S.} and Keeley, {Patrick W.} and Ecker, {Jennifer L.} and Mao, {Buqing Q.} and Johan Pahlberg and Bright Kim and Lee, {Sammy C.S.} and Fox, {Michael A.} and William Guido and Wong, {Kwoon Y.} and Sampath, {Alapakkam P.} and Reese, {Benjamin E.} and Rejji Kuruvilla and Samer Hattar",
note = "Funding Information: We thank Cara Altimus for help performing and analyzing wheel-running experiments, Andy Huberman for help with density recovery profile analysis, Richard Youle for antibody against activated Bax, Robert Margolskee for the antibody against γ13, and the late Dr. Stanley J. Korsmeyer for conditional Bax mice. Funding was provided by The Johns Hopkins University-Dean{\textquoteright}s office funds, The David and Lucile Packard Foundation Fellowship, The Alfred P. Sloan Fellowship, National Institutes of Health Grants R01-GM076430 and R01-EY019053 (to S.H.), National Institutes of Health Grant R01-MH080738 and a Whitehall Foundation Award (to R.K.), National Institutes of Health Grant R01-EY019968 (to B.E.R.), National Institutes of Health Grant R01-EY17606 and the McKnight Endowment Fund for Neuroscience (to A.P.S.), National Institutes of Health RO1-EY021222 (to M.A.F.) and -EY012716 (to W.G.), and a Scientific Career Development Award from Research to Prevent Blindness, National Institutes of Health Grant R00-EY18863, and the Kellogg Eye Center Core Grant P30-EY007003 (to K.Y.W.). ",
year = "2013",
month = feb,
day = "6",
doi = "10.1016/j.neuron.2012.11.028",
language = "English (US)",
volume = "77",
pages = "503--515",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",
}