Light has profound influences on many non-image forming (NIF) visual functions including circadian rhythms, sleep, mood, body temperature and the pupillary light reflex. In mammals, light influences these NIF functions through three retinal photoreceptors, namely the classical photoreceptors, rods and cones, and the intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin. As ganglion cells, ipRGCs integrate rod/cone input with their own intrinsic melanopsin-based phototransduction to serve as the sole conduits to signal light information to brain regions important for these NIF functions. However, how ipRGCs, a seemingly homogeneous population, integrate extrinsic light input from rods and cones with their own intrinsic melanopsin-based light responses to coordinate diverse behaviors is poorly understood. The overall goal of this competitive renewal is to address this fundamental question at three levels.
In Aim I, we will determine the functional circuits by which rod, cone and melanopsin-based signals are integrated in ipRGCs to drive NIF functions. Recently, we found that ipRGCs are much more diverse than previously appreciated, consisting of multiple morphologically and electrophysiologically distinct subtypes. Additionally, ipRGCs appear to be unique among retinal ganglion cells in that they co-express two neurotransmitters, glutamate and a neuropeptide, PACAP. Thus, in Aim II, we will define the relative contribution of glutamatergic and peptidergic neurotransmission to diverse NIF functions.
In Aim III, we will elucidate the functional contribution of individual ipRGC subtypes to NIF functions. These studies will advance our current understanding of the role of ipRGCs in controlling light- mediated behaviors that are essential to human health and a better quality of life.
Light has profound influence on human behaviors including the circadian alignment of physiology and behavior with the light-dark cycle. Disruptions in light-dependent behaviors results in numerous human health problems, including sleep disturbances, metabolic dysfunction, and depression. Our studies defining the retinal pathways by which light regulates essential behaviors are significant in promoting human health and a better quality of life.
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| Divya, Mundackal S; Rasheed, Vazhanthodi A; Schmidt, Tiffany et al. (2017) Intraocular Injection of ES Cell-Derived Neural Progenitors Improve Visual Function in Retinal Ganglion Cell-Depleted Mouse Models. Front Cell Neurosci 11:295 |
| Chen, Chih-Ming; Orefice, Lauren L; Chiu, Shu-Ling et al. (2017) Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice. Proc Natl Acad Sci U S A 114:E619-E628 |
| Dellapolla, Adriano; Kloehn, Ian; Pancholi, Harshida et al. (2017) Long days enhance recognition memory and increase insulin-like growth factor 2 in the hippocampus. Sci Rep 7:3925 |
| Chew, Kylie S; Renna, Jordan M; McNeill, David S et al. (2017) A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice. Elife 6: |
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