U19NS123719

Astrocyte Modulation of Neural Circuit Function and Behavior - Project Summary: Overall "What is the function of glial cells in neural centers? The answer is still not known, and it may remain unsolved for many years to come until scientists find direct methods to attack it." (Ramon y Cajal, 1901). This prophecy turned out to be accurate. Astrocytes, one of the most abundant cell types in the brain, have long been thought of as primarily passive support cells. Over the past two decades, studies indicate that astrocytes play pivotal roles in nervous system development, function, and diseases. However, a major unresolved issue in neuroscience is how astrocytes integrate diverse neuronal signals under healthy conditions, modulate neural circuit structure and function at multiple temporal and spatial scales, and how aberrant excitation and molecular output influences sensorimotor behavior and contributes to disease. The overall goal of this U19 team-research brain circuit program proposal is to address this fundamental issue by developing a deeper mechanistic understanding of astrocytes' roles in neural circuit operation, complex behaviors, and brain computation theories. Two overarching questions will be addressed: 1) How do astrocytes temporally and spatially integrate molecular signals from the diverse types of local and projection neurons activated during sensorimotor behaviors. 2) How do astrocytes convert this information into functional outputs that modulate neural circuit structure and function at different spatial and temporal scales. A multidisciplinary, comprehensive effort is proposed to address these questions that can only be completed through close collaboration between researchers with unique and complementary expertise. An innovative multi-scale approach integrating functional, anatomical, and genetic analyses with theoretical modeling will be leveraged. This approach involves quantitative behavioral assays, large-scale imaging of cellular and molecular dynamics, targeted cell-type-specific manipulations, high-throughput omic techniques, genetic profiling, protein engineering, machine learning, and computational modeling. By integrating experimental and theoretical approaches, molecular, cellular, and circuit mechanisms will be determined through which astrocytes influence neural circuits and contribute to complex behaviors and brain computation theories. The experimental and data analysis tools developed as part of this project will be invaluable for the broader neuroscience community.

San Diego, California Salk Institute For Biological Studies

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE 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. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND 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.

93.372 - 21st Century Cures Act - Brain Research through Advancing Innovative Neurotechnologies

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

La Jolla, California 92037 United States

Single Zip Code

BRAIN Initiative: Team-Research BRAIN Circuit Programs - TeamBCP (U19 Clinical Trial Not Allowed) (RFA-NS-19-003)

Amendment Since initial award the total obligations have increased 7979% from $132,623 to $10,714,074.