期刊
NEURON
卷 77, 期 3, 页码 503-515出版社
CELL PRESS
DOI: 10.1016/j.neuron.2012.11.028
关键词
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资金
- Johns Hopkins University-Dean's office funds
- David and Lucile Packard Foundation Fellowship
- Alfred P. Sloan Fellowship
- National Institutes of Health [R01-GM076430, R01-EY019053, R01-MH080738, R01-EY019968, R01-EY17606, RO1-EY021222, -EY012716, R00-EY18863]
- Whitehall Foundation
- McKnight Endowment Fund for Neuroscience
- Research to Prevent Blindness
- Kellogg Eye Center [P30-EY007003]
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. Box 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.
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