R01EY031597

Experience-Dependent Cellular Plasticity Mechanisms - Brain activity is essential for the development and plasticity of neurons and circuits, however our understanding of the mechanisms by which activity generates functional circuits is incomplete. This lack of knowledge impedes our ability to take advantage of activity-dependent mechanisms to facilitate circuit plasticity.

Plasticity-inducing stimuli induce neuronal protein dynamics, including regulated increases and decreases in protein synthesis. We recently conducted a quantitative in vivo proteomic analysis which identified changes in newly synthesized proteins in the Xenopus tadpole visual system in response to plasticity-inducing visual stimulation. We identified numerous candidate plasticity proteins (CPPs), including several that regulate protein synthesis, whereas others have diverse cellular and synaptic functions.

Here, we will probe the model that plasticity-inducing stimuli initiate a cascade of protein synthesis-dependent events, beginning with de novo synthesis of upstream translational regulators and culminating in the regulated synthesis of diverse effector proteins, in visual experience-dependent circuit plasticity in Xenopus. We will use proteomics, electrophysiology, in vivo structural and functional imaging, and behavioral assays.

Classical studies have revealed circuit-rewiring events in response to CNS damage. We have shown that local damage to the optic tectum impairs visual avoidance behavior in Xenopus and that treating injured animals with brief bouts of visual experience facilitates recovery of the injured circuit.

To probe the flexibility of experience-dependent plasticity mechanisms, we will test whether newly synthesized candidate plasticity proteins are required for the visual experience-dependent rehabilitation of the injured visuomotor circuit. Results of these experiments may identify novel mechanisms contributing to experience-dependent plasticity in developing nervous systems.

Scripps Research Institute

1) TO SUPPORT EYE AND VISION RESEARCH PROJECTS THAT ADDRESS THE LEADING CAUSES OF BLINDNESS AND IMPAIRED VISION IN THE U.S. THESE INCLUDE RETINAL DISEASES, CORNEAL DISEASES, CATARACT, GLAUCOMA AND OPTIC NEUROPATHIES, STRABISMUS, AMBLYOPIA, AND LOW VISION AND BLINDNESS REHABILITATION. 2) TO INCREASE UNDERSTANDING OF THE NORMAL DEVELOPMENT AND FUNCTION OF THE VISUAL SYSTEM IN ORDER TO BETTER PREVENT, DIAGNOSE, AND TREAT SIGHT-THREATENING CONDITIONS, AND, TO ENHANCE THE REHABILITATION, TRAINING, AND QUALITY OF LIFE OF INDIVIDUALS WHO ARE PARTIALLY-SIGHTED OR BLIND. 3) TO SUPPORT A BROAD PROGRAM OF BASIC VISION RESEARCH THROUGH GRANTS AND COOPERATIVE AGREEMENTS, TO ENCOURAGE HIGH QUALITY CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS, OTHER EPIDEMIOLOGICAL STUDIES, AND HEALTH SERVICES RESEARCH, TO ENCOURAGE RESEARCH TRAINING AND CAREER DEVELOPMENT IN THE SCIENCES RELATED TO VISION, AND TO SPONSOR SCIENTIFIC WORKSHOPS IN HIGH PRIORITY RESEARCH AREAS TO ENCOURAGE EXCHANGE OF INFORMATION AMONG SCIENTISTS. 4) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENCOURAGE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.867 - Vision Research

National Eye Institute (NEI) [HHS - NIH]

California United States

State-Wide

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 423% from $683,732 to $3,578,100.