A significant percentage of people in the US suffer from disabilities resulting from traumatic injury, stroke, or degenerative disease which result in deficits in visual perception. Therefore, an understanding of the basic circuit neurobiology and neuromodulation of feature-based visual perception will sharpen our understanding of the mechanism of visual processing, and should facilitate the development of treatments for these disabilities. One form of visual attention is targeted to salient features of the visual scene, durng which a subject detects spatio-temporal disparities that distinguish a feature from a cluttered visual surround. The cell-circuit mechanism for how this occurs is not well understood. This project will capitalize on the significant experimental advantages of the fruit fly Drosophila to explore the neural circuits that produce an elementary analogue of feature-based visual attention. The fly has a numerically simple nervous system, with which highly advanced genetic techniques can be used to identify, manipulate, and repeatedly record the activity of individual neurons, as well as their upstream and downstream network partners. The fly also displays robust feature-based visual perception, even under stimulus conditions that defeat classical models of motion vision, for which similar processes have been localized to cortical pathways in humans and non-human primates. The PI hypothesizes that flies detect and process these higher-order features with specialized circuits that integrate first-order elementary motion signals with parallel higher-order spatiotemporal disparities, each of which are sculpted by the action of inhibitory neurotransmitters. The PI will perform two-photon Ca2+ imaging of candidate cellular pathways in response to stimuli the PI has discovered to elicit robust higher-order feature detection by flies within a virtual reality flight simulator. Armed with physiological receptive fields, the PI will examine how feature perception observed during active flight behavior is perturbed by optogenetically silencing these circuits and testing the effects using a systems identification technique that extracts input-output functions of first-order and higher-order feature vision from an intact behaving fly. Finally, the PI will study how specific inhibitor neurotransmitters such as GABA and glutamate sculpt the physiology of feature coding neurons and feature attention behavior.

Public Health Relevance

Healthy vision is crucial for everyday life and healthspan. Disorders and disruptions to visual processing from disease and traumatic injury lead to disabilities affect a significant population of the United States. The proposed project will use a genetic model system to study the cell-circuit mechanisms for normal feature-based visual perception, as well as how deficits are caused and ameliorated. The proposed research is expected to facilitate broader understanding of normal visual function

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY026031-04
Application #
9684623
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Flanders, Martha C
Project Start
2016-05-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Mongeau, Jean-Michel; Frye, Mark A (2017) Drosophila Spatiotemporally Integrates Visual Signals to Control Saccades. Curr Biol 27:2901-2914.e2
Kele?, Mehmet F; Frye, Mark A (2017) Object-Detecting Neurons in Drosophila. Curr Biol 27:680-687
Omoto, Jaison Jiro; Kele?, Mehmet Fatih; Nguyen, Bao-Chau Minh et al. (2017) Visual Input to the Drosophila Central Complex by Developmentally and Functionally Distinct Neuronal Populations. Curr Biol 27:1098-1110