title: Retinal Waves Modulate an Intraretinal Circuit of Intrinsically Photosensitive Retinal Ganglion Cells.
abstract: Before the maturation of rod and cone photoreceptors, the developing retina relies on light detection by intrinsically photosensitive retinal ganglion cells (ipRGCs) to drive early light-dependent behaviors. ipRGCs are output neurons of the retina; however, they also form functional microcircuits within the retina itself. Whether ipRGC microcircuits exist during development and whether they influence early light detection remain unknown. Here, we investigate the neural circuit that underlies the ipRGC-driven light response in developing mice. We use a combination of calcium imaging, tracer coupling, and electrophysiology experiments to show that ipRGCs form extensive gap junction networks that strongly contribute to the overall light response of the developing retina. Interestingly, we found that gap junction coupling was modulated by spontaneous retinal waves, such that acute blockade of waves dramatically increased the extent of coupling and hence increased the number of light-responsive neurons. Moreover, using an optical sensor, we found that this wave-dependent modulation of coupling is driven by dopamine that is phasically released by retinal waves. Our results demonstrate that ipRGCs form gap junction microcircuits during development that are modulated by retinal waves; these circuits determine the extent of the light response and thus potentially impact the processing of early visual information and light-dependent developmental functions.
  
  
  
  Light-dependent functions in early development are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Here we show that ipRGCs form an extensive gap junction network with other retinal neurons, including other ipRGCs, which shapes the retina's overall light response. Blocking cholinergic retinal waves, which are the primary source of neural activity before maturation of photoreceptors, increased the extent of ipRGC gap junction networks, thus increasing the number of light-responsive cells. We determined that this modulation of ipRGC gap junction networks occurs via dopamine released by waves. These results demonstrate that retinal waves mediate dopaminergic modulation of gap junction networks to regulate pre-vision light responses.
authors.affiliation: Department of Molecular and Cell Biology.
authors.forename: David A
authors.identifier: 0000-0002-5398-3595
authors.initials: DA
authors.lastname: Arroyo
authors.affiliation: Biophysics Graduate Group, and.
authors.forename: Lowry A
authors.identifier: 0000-0003-2164-1790
authors.initials: LA
authors.lastname: Kirkby
authors.affiliation: Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, California 94720-3200 mfeller@berkeley.edu.
authors.forename: Marla B
authors.identifier: 0000-0002-9137-5849
authors.initials: MB
authors.lastname: Feller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010775:Photic Stimulation; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000099210:Melanopsin
chemical_list: D001710:Biotin; D004079:Dihydro-beta-Erythroidine; D004298:Dopamine; D018377:Neurotransmitter Agents; D017299:Rod Opsins; D050819:Transcription Factor Brn-3A; D014446:Tyrosine 3-Monooxygenase; D005680:gamma-Aminobutyric Acid; D000099210:Melanopsin; C494189:Pou4f1 protein, mouse; C070614:neurobiotin
keywords: CNiFER; amacrine; electrical synapses; nicotinic acetylcholine receptor