U19NS123714

Thalamus in the Middle: Computations in Multi-Regional Neural Circuits - Summary, Overall

This collaborative project aims to uncover the logic of signal routing from subcortical areas to the frontal cortex through the thalamus. The frontal cortex displays rich patterns of neural activity, which can be decomposed into "activity modes" that correspond to specific aspects of behavior. Examples include the persistent activity correlated with short-term memory and motor planning, and the rapidly oscillating activity during voluntary movements.

In this dynamical systems perspective of neural computation, complex behaviors correspond to distinct sequences of cortical activity modes. However, the cortex does not generate these activity modes in isolation, but instead is strongly and bidirectionally coupled to the thalamus, the central hub of the forebrain. Most of the thalamus is non-sensory ("higher-order"), receiving subcortical input from the cerebellum, midbrain, and hippocampus.

Our central theory is that these subcortical signals flow through higher-order thalamus to reach the frontal cortex, where they enable activity modes, update activity modes, and cause switching between modes, akin to the "update" and "reset" signals in long short-term memory networks in machine learning. However, most of what we know about thalamus comes from sensory systems, and our knowledge of subcortex thalamus frontal cortex circuits is nascent.

We still have only a rudimentary understanding of the input and output circuits of higher-order thalamus, the morphology and molecular properties of thalamic neurons, the circuit motifs that link subcortical input to cortical activity, and the engagement of these networks across the frontal cortex. We bring together a team with expertise in modern high-throughput anatomy (Project 1, 2), molecular neuroscience (Project 2, Molecular Science Core), cellular and synaptic neurophysiology (Project 3), large-scale neurophysiology in mice performing behaviors that require short-term memory and decision-making (Project 3, 4), and theory and computation (Project 5, Data Science Core).

We will collaborate to uncover how information flows from subcortical areas, through thalamus, to control cortical activity modes and thereby shape behavior. Individual projects are guided by a conceptual framework of multi-regional neural computation, placing the thalamus in the middle of a multi-regional neural network. Together, our work will have broad implications for the understanding of neural computation in subcortex thalamus cortex circuits and will produce anatomy-guided multi-regional circuit models of cognitive function.

We will also produce paradigm-shifting community resources, including quantitative anatomy, novel genetic reagents, neurophysiological data, and a rich modeling framework, upon which future studies of thalamic circuits will be built.

Allen Institute

(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 981094307 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 319% from $3,700,000 to $15,510,934.