U01NS131810

Integrative Circuit Dissection in the Behaving Nonhuman Primate

In natural vision, recognizing objects based on the retinal image is challenging and is often an ill-posed problem because a single image is compatible with multiple interpretations. Nevertheless, the primate brain has a remarkable ability to understand ambiguous scenes and solve difficult object recognition problems. Converging evidence suggests that this process, especially in challenging contexts—e.g., occlusion or low-visibility environments—is based on the integration of sensory information with prior knowledge built from experience.

Our goal is to develop circuit diagrams at a cellular level that specify how inter-areal interactions support the integration of sensory signals related to the visual image with internal models that represent prior knowledge, thereby revealing the computations that underlie scene understanding, object recognition, and perceptual decision making in the primate brain.

To achieve this goal, we have assembled a synergistic team of experts to bring together:

(I) Viral-based circuit tracing and optogenetic methods to identify connected neurons;
(II) Multiphoton imaging and high-density electrode recordings to functionally characterize neurons and signaling motifs in the awake macaque monkey;
(III) Behavioral manipulations; and
(IV) Cutting-edge computational modeling to reveal how systems of connected neurons across brain regions interact and support complex perceptual processes.

Our proposal includes four projects.

In Project 1, PI Briggs will lead an effort to establish circuit tracing protocols to support dense, reliable, and long-term tracking of connected neurons in the macaque monkey. We will histologically compare lentivirus and AAVretro constructs in terms of their efficacy, toxicity, directional reliability, layering, and spread in labeling connected neurons. Additionally, we will test opto-tagging using high-density neurophysiology.

In Projects 2 & 3, PI Bair will lead the effort to implement multiphoton imaging in the awake monkey to identify projecting neurons in vivo during the simultaneous physiological characterization of hundreds of neurons down to a depth of approximately 1 mm in cortex.

In Project 4, PI Pasupathy will lead the effort to apply the viral methods and physiological characterization with high-density Neuropixels probes and multiphoton imaging to study neurons in visual cortex (Area V4), prefrontal cortex, and the visual pulvinar as macaque monkeys perform shape detection in impoverished images.

PI Wu will lead the effort to interpret the population dynamics in the context of communication subspace models and reveal how connected neurons in three brain regions underlie the multiplexing of sensory signals and prior knowledge to facilitate object detection and scene understanding.

University Of Washington

(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]

Seattle, Washington 981950009 United States

Single Zip Code

BRAIN Initiative: Exploratory Team-Research BRAIN Circuit Programs - eTeamBCP (U01 Clinical Trials Optional) (RFA-NS-22-028)

Amendment Since initial award the total obligations have increased 163% from $1,179,636 to $3,101,478.