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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / physiology
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Action Potentials / radiation effects
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Alcohol Oxidoreductases
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Animals
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Apoptosis / genetics
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Apoptosis / physiology*
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Basic Helix-Loop-Helix Transcription Factors / deficiency
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Biophysical Phenomena
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Circadian Rhythm / genetics
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Circadian Rhythm / physiology*
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Co-Repressor Proteins
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DNA-Binding Proteins / metabolism
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Female
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Gene Expression Regulation / genetics
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Gene Expression Regulation / radiation effects
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Green Fluorescent Proteins / genetics
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In Situ Nick-End Labeling
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In Vitro Techniques
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Light Signal Transduction / physiology
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Light Signal Transduction / radiation effects
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Motor Activity / genetics
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Motor Activity / radiation effects
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / metabolism
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Phosphoproteins / metabolism
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Photic Stimulation
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Proto-Oncogene Proteins c-fos / metabolism
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Retinal Cone Photoreceptor Cells / physiology*
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Retinal Ganglion Cells / physiology*
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Retinal Rod Photoreceptor Cells / physiology*
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Rod Opsins / metabolism
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Tyrosine 3-Monooxygenase / metabolism
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Visual Pathways / physiology
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bcl-2 Homologous Antagonist-Killer Protein / deficiency
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bcl-2-Associated X Protein / deficiency
Substances
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Atoh7 protein, mouse
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Bak1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Bax protein, mouse
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Bsn protein, mouse
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Co-Repressor Proteins
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DNA-Binding Proteins
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Nerve Tissue Proteins
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Phosphoproteins
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Proto-Oncogene Proteins c-fos
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Rod Opsins
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-2-Associated X Protein
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melanopsin
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Green Fluorescent Proteins
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Alcohol Oxidoreductases
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Ctbp2 protein, mouse
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Tyrosine 3-Monooxygenase