Past work under this grant documented the existence of a peculiar type of mammalian ganglion cell that functions as an autonomous photoreceptor. These intrinsically photosensitive retinal ganglion cells (ipRGCs) use the invertebrate-like photopigment melanopsin. They encode ambient light intensity and help to drive various reflexive responses to daylight, such resetting the circadian clock and adjusting pupil diameter. Much of the work in the next grant period is inspired by two surprising lines of pilot evidence. First, we now believe that there is at least one additional type of intrinsically photosensitive ganglion cell. Second, we have evidence that signals from ganglion-cell photoreceptors propagate not only to the non-image-forming visual networks of the brain, but also within the eye itself to other retinal neurons. Targets appear to include certain ganglion cells and dopaminergic amacrine (DA) cells. The influence of ipRGCs on DA cells is apparently reciprocated, and we will study the mutual interactions between these cells in detail. DA cells and ipRGCs are further linked by the fact that both stratify in the same OFF sublamina of the IPL, yet receive a paradoxical synaptically driven ON input of unknown origin. Here, we will work to identify a neural circuit that could account for this input.
The specific aims of the proposal are: 1) to characterize the structure and function of a new type of ganglion-cell photoreceptor;2) to characterize the inputs to ipRGCs from dopaminergic amacrine cells and ON bipolar cells;and 3) to characterize the influences of ipRGCs on dopaminergic amacrine cells and other retinal neurons. These studies extend our understanding of the photoreceptive capacity that persists in human outer retinal degenerations such as retinitis pigmentosa. They also bear on fundamental mechanisms of circadian and adaptation modulation of retinal function.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY012793-11S1
Application #
8195278
Study Section
Special Emphasis Panel (ZRG1-CB-G (90))
Program Officer
Greenwell, Thomas
Project Start
2000-02-07
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
11
Fiscal Year
2011
Total Cost
$99,231
Indirect Cost
Name
Brown University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
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Sabbah, Shai; Berg, Daniel; Papendorp, Carin et al. (2017) A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks. eNeuro 4:
Sabbah, Shai; Gemmer, John A; Bhatia-Lin, Ananya et al. (2017) A retinal code for motion along the gravitational and body axes. Nature 546:492-497
Walker, Marquis T; Rupp, Alan; Elsaesser, Rebecca et al. (2015) RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells. Mol Biol Cell 26:3671-8
Renna, Jordan M; Chellappa, Deepa K; Ross, Christopher L et al. (2015) Melanopsin ganglion cells extend dendrites into the outer retina during early postnatal development. Dev Neurobiol 75:935-46
Lucas, Robert J; Peirson, Stuart N; Berson, David M et al. (2014) Measuring and using light in the melanopsin age. Trends Neurosci 37:1-9
Dhande, Onkar S; Estevez, Maureen E; Quattrochi, Lauren E et al. (2013) Genetic dissection of retinal inputs to brainstem nuclei controlling image stabilization. J Neurosci 33:17797-813
Weng, Shijun; Estevez, Maureen E; Berson, David M (2013) Mouse ganglion-cell photoreceptors are driven by the most sensitive rod pathway and by both types of cones. PLoS One 8:e66480
Van Hook, Matthew J; Wong, Kwoon Y; Berson, David M (2012) Dopaminergic modulation of ganglion-cell photoreceptors in rat. Eur J Neurosci 35:507-18
Estevez, Maureen E; Fogerson, P Michelle; Ilardi, Marissa C et al. (2012) Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision. J Neurosci 32:13608-20

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