DP1NS127279

Emergence of Activity Patterns in the Cerebral Cortex and Their Influence on Brain Circuit Development and Function - Project Summary/Abstract

Brain function requires coordinated activation of specific networks engaged in systems that process information in localized and distributed manners. In order to develop such specific networks, the brain engages groups of neurons that fire together in ensembles that can be observed with calcium imaging.

Patterns of spontaneous activity in the cerebral cortex are thought to enable the formation of circuits specialized for processing different types of sensory information. However, how the brain first switches on activity across areas is unknown. This project aims to investigate exactly how and when in fetal life these patterns first occur in vivo, what regulates their development, and how they shape neural circuits and later brain function.

A major barrier to addressing this question has been that patterns of activity such as patchwork-type activity in S1 and traveling waves in V1 are present at birth in rodents, making it difficult to study this question in vivo as the brain apparently switches on before birth. To address this, the researcher proposes to apply modern scientific tools and technologies to an Australian marsupial mammal: the fat-tailed dunnart (S. crassicaudata; Dasyuridae), thereby developing a new approach for investigating brain development.

Dunnarts are small carnivorous animals whose pups (joeys) are born at an equivalent stage of development to embryonic day 10 in mice or seven-week gestation in humans. Therefore, most of their brain development occurs as they develop inside their mother's pouch. Despite this more primitive developmental phase, dunnarts have a six-layered cerebral cortex which is similar to a mouse but with advantageous exceptions such as a more advanced binocular visual system. Dunnarts are also able to solve complex configurable problems and learn quickly.

To ensure the feasibility of this project, the researcher provides evidence that targeted electroporation can be used to introduce sensitive calcium indicators such as GCAMP6S into the cortex. In preliminary experiments, it is found that patchwork-type activity in S1 and traveling waves in V1 are evolutionarily conserved in dunnarts, motivating this new direction of research to understand the development and function of these patterns of spontaneous activity.

Having access to study the entire genesis and development of these patterns enables longitudinal studies that can link cells, circuits, and behavior/function. The creation of longitudinal imaging capabilities bridging micro/meso/macro scales as well as awake behavior across the lifespan will be required in order to identify which neuronal cell types initiate spontaneous synchronous activity and whether these activity patterns are instructive in forming functionally-specific circuits. The researcher will also explore how spontaneous activity in the cortex evolves throughout life as circuits begin to function to mediate sensory experience and behavioral reactions.

By understanding the fundamental processes required to build patterned activity in the brain and how these affect behavior, this work will advance our knowledge of the neural basis of mental experience.

Washington University

(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.

93.310 - Trans-NIH Research Support

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

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Saint Louis, Missouri 631101010 United States

Single Zip Code

NIH Directors Pioneer Award Program (DP1 Clinical Trial Optional) (RFA-RM-20-011)

Amendment Since initial award the total obligations have increased 396% from $1,102,500 to $5,468,166.