The effects of sleep and iPRGCs on computations in the early visual system

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.

Grant Number: 5F32EY036275-03
NIH Institute/Center: NIH
Principal Investigator: David Au