PROJECT SUMMARY/ABSTRACT Vision is an important driver of our evolution and adaptation to different environments. It is a complex process that begins with photoreceptor signal transduction in retinal circuitry before transmitting to central brain targets to drive a range of image-forming visual functions, from color discrimination to navigation. Canonically, studies on image forming vision in the retina and cortex have largely focused on rod and cone inputs that encode pattered visual images. However, additional inputs that contribute to complex retinal and cortical computations from melanopsin-expressing intrinsically photosensitive retinal ganglion cells (iPRGCs) or sleep are largely unexplored. Therefore, there is a need to understand how multiplexed photoreceptor inputs mediate retinal and cortical processes and how such responses are altered with sleep. I hypothesize that multiplexing of rod, cone, and melanopsin input will allow cortical neurons to respond to visual stimuli with a large range of irradiance under complex visual features like natural scenes, and that these processes will be modulated by sleep. My objectives are to measure melanopsin-specific retinal and cortical responses, use that information to build a predictive computational model of the early visual system that incorporates multiplexed photoreceptor inputs, and determine how sleep alters cortical computations for visual processing. I will begin by isolating and measuring melanopsin-specific responses in the retina and cortex under natural scenes in Aim 1. Then, I will record responses in the visual cortex under natural scenes at different points of circadian time-of-day and sleep deprivation in Aim 2. By understanding a detailed quantitative description of how visual experience is represented in the retina and visual cortex, we will better understand how and why vision loss occurs in diseases and disorders that affect the early visual system. Furthermore, my work will contribute to the development of accurate and sophisticated computational models that could improve the design of cortical prosthesis systems that aim to restore lost vision due to damages or disorders to the visual centers of the brain. My Sponsor, Dr. Stephen Baccus, and I have created a training plan to focus on developing my technical, writing and communication, and mentorship skills. My technical skills will focus heavily on in vivo and in vitro electrophysiology, microscopy, behavioral assays, computational analysis, and computational modeling. I plan to register for relevant courses, attend workshops and training events, and network with experts in the field. My writing and communication skills will be developed by applying for grants/fellowships, manuscript development, and presenting at conferences. I will develop my mentorship skills by training undergraduate and graduate students to help run experiments and analyze data. I am part of a highly collaborative research environment with many world renown experts in the visual neurosciences within my department and sleep neurosciences through collaborations with adjacent departments. I plan to fully utilize the resources and facilities available to accomplish the goals of this proposal, as well as achieve my goal of becoming an independent research scientist.

PROJECT NARRATIVE/RELEVANCE Mammalian rod, cone, and melanopsin photoreceptors contribute to image-forming visual processes that encode complex computations in the retina and cortex. Vision also influences behaviors like sleep, which result in feedback mechanisms that enable sleep as a neuromodulator to the cortical neural code. Understanding how multiplexed photoreceptor systems and sleep modulate cortical computations driven by complex visual stimuli could lead to the development of more sophisticated computational models that help improve the design of cortical prostheses.