title: Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype.
abstract: BACKGROUND
  Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. In early development these cells mediate different processes, including negative phototaxis and the timing of retinal vascular development. To determine if ipRGC physiologic properties also change with development, we measured ipRGC cell density and light responses in wild-type mouse retinas at post-natal days 8, 15 and 30.
  
  
  RESULTS
  Melanopsin-positive cell density decreases by 17% between post-natal days 8 and 15 and by 25% between days 8 and 30. This decrease is due specifically to a decrease in cells co-labeled with a SMI-32, a marker for alpha-on ganglion cells (corresponding to adult morphologic type M4 ipRGCs). On multi-electrode array recordings, post-natal day 8 (P8) ipRGC light responses show more robust firing, reduced adaptation and more rapid recovery from short and extended light pulses than do the light responses of P15 and P30 ipRGCs. Three ipRGC subtypes - Types I-III - have been defined in early development based on sensitivity and latency on multielectrode array recordings. We find that Type I cells largely account for the unique physiologic properties of P8 ipRGCs. Type I cells have previously been shown to have relatively short latencies and high sensitivity. We now show that Type I cells show have rapid and robust recovery from long and short bright light exposures compared with Type II and III cells, suggesting differential light adaptation mechanisms between cell types. By P15, Type I ipRGCs are no longer detectable. Loose patch recordings of P8 M4 ipRGCs demonstrate Type I physiology.
  
  
  CONCLUSIONS
  Type I ipRGCs are found only in early development. In addition to their previously described high sensitivity and rapid kinetics, these cells are uniquely resistant to adaptation and recover quickly and fully to short and prolonged light exposure. Type I ipRGCs correspond to the SMI-32 positive, M4 subtype and largely lose melanopsin expression in development. These cells constitute a unique morphologic and physiologic class of ipRGCs functioning early in postnatal development.
authors.affiliation: Department of Ophthalmology, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA. tsexton@uw.edu.|Program in Neurobiology and Behavior, University of Washington, Health Sciences Center, Seattle, WA, 98195, USA. tsexton@uw.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sexton
authors.affiliation: Department of Biological Structure, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. bleckert@uw.edu.|Program in Neurobiology and Behavior, University of Washington, Health Sciences Center, Seattle, WA, 98195, USA. bleckert@uw.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Bleckert
authors.affiliation: Department of Physiology & Biophysics, University of Washington, 1705 NE Pacific St., Seattle, WA, 98195, USA. mhturner@uw.edu.|Program in Neurobiology and Behavior, University of Washington, Health Sciences Center, Seattle, WA, 98195, USA. mhturner@uw.edu.
authors.forename: Maxwell H
authors.initials: MH
authors.lastname: Turner
authors.affiliation: Department of Ophthalmology, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA. russvg@uw.edu.|Department of Biological Structure, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. russvg@uw.edu.|Department of Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. russvg@uw.edu.|Program in Neurobiology and Behavior, University of Washington, Health Sciences Center, Seattle, WA, 98195, USA. russvg@uw.edu.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Van Gelder
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*