The long-term goal of this proposal is to characterize the connectivity of specific circuits in the mouse visual system whose gross architecture is highly conserved across species from mouse to primate. The objective is to identify the neural circuits that transmit visual information from the retina, through different regions of the dorsal lateral geniculate nucleus (dLGN), to specific populations of neurons in the primary visual cortex (V1) that contribute to visual perception and behavior. The central hypotheses of this proposal are: (1) that neurons in the shell and core of the dLGN receive different types of visual information from the retina and, therefore, can transmit different types of visual information to V1 neurons; (2) The balance of core and shell input that V1 neurons receive influences their tuning properties. The experiments outlined in this proposal will test these hypotheses by pursuing three specific aims: (1) Identifying and characterizing the retinal ganglion cell (RGC) types that provide input to neurons in the core of the dLGN, as well as the neurons that those dLGN neurons contact in V1; (2) Determining whether genetically-identified neurons in V1 receive input from unique patterns of RGCs; and (3) Determining how input from neurons in the core of the dLGN influence tuning properties in genetically-identified populations of V1 neurons. This proposal is technologically innovative; it will use novel mouse lines as well as a combination of rabies circuit tracing, whole-cell recording, optogenetic stimulation, chemogenetic silencing, and two-photon calcium imaging to accomplish its aims. The proposed research will yield significant findings that will provide considerable insight into how information is encoded, processed, and ultimately transmitted throughout the mouse visual pathway. These findings are of utmost importance as the computations performed in these pathways generate a representation of the visual scene and ultimately make characteristic contributions to perception and behavior. The proposed research will also help determine the extent to which visual processing in the mouse visual system does, or does not, mimic visual processing in the primate visual system. Understanding the extent to which computations performed in the visual pathway overlap in mouse and primate visual systems is critical for determining how research done in in the mouse visual system translates to the primate ? and therefore human ? visual system. Indeed, to successfully develop strategies to restore sight across a wide range of afflictions of the visual system, it is critical to first understand how the visual system gives rise to our sense of the world around us. The work proposed here will unequivocally move us closer to this goal.

Public Health Relevance

This proposal seeks to understand how information about the world around us is transmitted from the eye to the brain. In particular, the scope of work of this project seeks to develop a complete understanding, at the level of cells and neural circuits, of how visual information is detected and processed by the visual system to give rise to our perception of the world around us and, ultimately, our behavior. The discoveries made by this proposal will speed the advent of therapies designed to treat damage and diseases that afflict the visual system and lead to blindness.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY031517-01
Application #
9961274
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Flanders, Martha C
Project Start
2020-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037