SHIH-KUO CHEN2018-09-102018-09-102013-02-06http://www.scopus.com/inward/record.url?eid=2-s2.0-84873293021&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/377587The 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 networkenMelanopsinAtoh7 ProteinMouseBak1 ProteinBasic Helix-loop-helix Transcription FactorsBax ProteinBsn ProteinCtbp2 ProteinDna-binding ProteinsGreen Fluorescent ProteinsNerve Tissue ProteinsPhosphoproteinsProto-oncogene Proteins C-fosRod OpsinsTyrosine 3-monooxygenaseBcl-2 Homologous Antagonist-killer ProteinBcl-2-associated X ProteinProtein BaxProtein C FosAnimal CellAnimal ExperimentApoptosisArticleCircadian RhythmControlled StudyDendriteFemaleIntrinsically Photosensitive Reitnal Ganglion CellLight IrradianceMaleNerve Cell NetworkNewbornNonhumanPhotobiologyPhotoentrainmentPhotosensitivityPriority JournalRetina ConeRetina Ganglion CellRetina RodSensory System ElectrophysiologySynapseAction PotentialsAnimalsBiophysical ProcessesGene Expression RegulationIn Situ Nick-end LabelingLight Signal TransductionMiceInbred C57blKnockoutMotor ActivityPhotic StimulationRetinal Cone Photoreceptor CellsRetinal Ganglion CellsRetinal Rod Photoreceptor CellsVisual Pathwaysjournal article10.1016/j.neuron.2012.11.028