Apoptosis Regulates ipRGC Spacing Necessary for Rods and Cones to Drive Circadian Photoentrainment
Journal
Neuron
Journal Volume
77
Journal Issue
3
Pages
503-515
Date Issued
2013-02-06
Author(s)
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
Subjects
Melanopsin
Atoh7 Protein
Mouse
Bak1 Protein
Basic Helix-loop-helix Transcription Factors
Bax Protein
Bsn Protein
Ctbp2 Protein
Dna-binding Proteins
Green Fluorescent Proteins
Nerve Tissue Proteins
Phosphoproteins
Proto-oncogene Proteins C-fos
Rod Opsins
Tyrosine 3-monooxygenase
Bcl-2 Homologous Antagonist-killer Protein
Bcl-2-associated X Protein
Protein Bax
Protein C Fos
Animal Cell
Animal Experiment
Apoptosis
Article
Circadian Rhythm
Controlled Study
Dendrite
Female
Intrinsically Photosensitive Reitnal Ganglion Cell
Light Irradiance
Male
Nerve Cell Network
Newborn
Nonhuman
Photobiology
Photoentrainment
Photosensitivity
Priority Journal
Retina Cone
Retina Ganglion Cell
Retina Rod
Sensory System Electrophysiology
Synapse
Action Potentials
Animals
Biophysical Processes
Gene Expression Regulation
In Situ Nick-end Labeling
Light Signal Transduction
Mice
Inbred C57bl
Knockout
Motor Activity
Photic Stimulation
Retinal Cone Photoreceptor Cells
Retinal Ganglion Cells
Retinal Rod Photoreceptor Cells
Visual Pathways
Type
journal article