One function of the visual system is to enable conscious perception of spatial details in tlie environment;this requires the rod and cone photoreceptor cells in the retina. The visual system also mediates subconscious, non-image-forming photic regulation of various physiological functions such as the pupil reflex and the resetting of our body clocks to the solar cycle. Failure to properly regulate these accessory visual responses results in a wide range of health problems including depression, sleep disorders, and even' cancer. Non-image-forming photoreception utilizes not only rods and cones but also the recently discovered ganglion-cell photoreceptors, i.e. the intrinsically photosensitive retinal ganglion cells (ipRGCs), Recent studies suggested that ipRGCs Interact bidirectionally with other retinal neurons: bipolar and amacrine cells feed rod/cone-driven light responses to ipRGCs, vifhile these ganglion cells signal their intrinsic photoresponses to bipolar and amacrine cells. This grant uses electrophysiological and imaging methods to study both directions of synaptic interactions In rodent retinas and comprises three goals: (1) To Identify ON bipolar cells that innervate the ipRGCs and analyze their light responses, through intracellular recordings from ON bipolar cells followed by fluorescence Imaging of intracellular dye fills;(2) To analyze the effects of amacrine-csll neuromodulators on ipRGCs, by testing chemicals that either activate or inhibit the receptors for these neuromodulators;and (3) To Identify bipolar and amacrine cells that receive synaptic Input from ipRGCs, by using intracellular recordings to search for light-sensitive bipolar and amacrine cells in rodless coneless retinas. Findings from these studies will enable a better understanding of how rod/cone signals regulate our body docks, the pupil reflex and other non-image-forming photosensory behaviors, and will also provide clues as to how the ipRGCs might modulate rod/cone circuits and hence conscious visual perception. This new knowledge may be useful for the development of drugs and light therapies for sleep problems and depression, the design of better workplace policies and school schedules to promote alertness and maximize productivity, and the development of healthier lighting technologies.

Public Health Relevance

Neuronal circuits for conscious visual perception and for non-image-forming behavioral responses to light (eg. sleep timing, alertness, and the pupil reflex) interact in the retina. This grant analyzes the physiology of such interactions. The findings may help the development of better therapies for sleep disorders and depression, and of better lighting designs to enhance productivity at work and in school.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Greenwell, Thomas
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Zhao, Xiwu; Stafford, Ben K; Godin, Ashley L et al. (2014) Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells. J Physiol 592:1619-36
Hu, Caiping; Hill, Dijon D; Wong, Kwoon Y (2013) Intrinsic physiological properties of the five types of mouse ganglion-cell photoreceptors. J Neurophysiol 109:1876-89
Chen, Shih-Kuo; Chew, Kylie S; McNeill, David S et al. (2013) Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron 77:503-15