Optogenetics refers to a cutting-edge set of molecular methods that allows for light-based control of targeted neurons in intact brains. These methods have immense potential as a basic research tool to determine the role of specific neuronal populations in healthy and abnormal brain function. In addition, further development of these methods may lead to new types of treatments for neurological and psychiatric disorders, as well as a new class of prostheses for those with sensory impairments. This project is aimed at further developing these methods so that they can achieve their basic research and clinical potential. This proposal introduces key improvements in the molecular methods as well as fundamental improvements in their application to the study of higher-order perceptual and cognitive functions. Critically, the approach of this proposal is minimally invasive and hence, unlike previous methods, causes little to no tissue damage. In addition, the improvements introduced by this proposal allow for more precise targeting of neurons and more potent control of the responses of those neurons. This proposal uses these methods to systematically determine their efficacy at both the neuronal and the behavioral levels. A key innovation of this approach is the development of an """"""""optogenetic window"""""""". This window will permit long-term health of the cortex, functional mapping prior to delivery of molecular agents, precise targeting of molecular agents to specific functional sites, and assessment with established optical imaging, electrophysiological, and behavioral methods. This proposal will allow patterns of neuronal modulation (both inhibitory and excitatory) to be related to specific perceptual and behavioral effects. The successful completion of this project will have enormous benefits for basic research into higher-order perceptual and cognitive functions, and will provide a solid foundation for the development of new treatments for the sensory impaired as well as those with psychiatric or neurological disorders.

Public Health Relevance

The long-term goal of this project is to provide insight into the neuronal mechanisms that underlie perception and cognition. This project will provide methods and knowledge that will aid in the treatment and prevention of neurological and psychiatric disorders. These aims are also directly relevant to the development of prostheses for the visually handicapped.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY022853-02
Application #
8550071
Study Section
Special Emphasis Panel (ZRG1-IFCN-L (02))
Program Officer
Steinmetz, Michael A
Project Start
2012-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$207,813
Indirect Cost
$55,813
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Chernov, Mykyta M; Friedman, Robert M; Chen, Gang et al. (2018) Functionally specific optogenetic modulation in primate visual cortex. Proc Natl Acad Sci U S A 115:10505-10510
Roe, Anna Wang; Chernov, Mykyta M; Friedman, Robert M et al. (2015) In Vivo Mapping of Cortical Columnar Networks in the Monkey with Focal Electrical and Optical Stimulation. Front Neuroanat 9:135
Nassi, Jonathan J; Avery, Michael C; Cetin, Ali H et al. (2015) Optogenetic Activation of Normalization in Alert Macaque Visual Cortex. Neuron 86:1504-17
Ruiz, Octavio; Lustig, Brian R; Nassi, Jonathan J et al. (2013) Optogenetics through windows on the brain in the nonhuman primate. J Neurophysiol 110:1455-67