UM1MH136462

Optimization of genetically encoded voltage and neurotransmitter indicators for multiwavelength in vivo analysis of brain circuits - the brain is remarkably dynamic, adaptive, and flexible in response to environmental changes. These capacities are enabled by diverse cell types which communicate with an array of chemical neurotransmitters (NTs) or neuromodulators (NMs) and receptors.

Neurochemical inputs have a wide-ranging and dramatic influence on neuronal activity and circuit dynamics. To understand the logic by which multiple convergent inputs shape neuronal activity, it is essential to record the timing and location of NT and NM release and the dynamic changes in membrane voltage that result. Our team has developed genetically encoded indicators, as well as high-speed and resolution microscopy, to allow simultaneous optical measurement of various NT/NM release and diffusion and post-synaptic activity in vivo with cell-type and circuit specificity.

Broad applications of these technologies have started to reveal how neuromodulators collectively manipulate brain-wide states. Despite these successes, significant headroom exists to optimize these indicators to enable sensitive imaging in small structures, higher throughput, and measurements in sparsely-innervated brain areas.

Moreover, existing NT and voltage indicators are nearly all green in color, and optimization of other colors is needed to enable multiplexing, along with hardware to perform such recordings and algorithms to process them. Finally, these new tools must be rigorously and systematically benchmarked in vivo to allow the large community of users to better design and interpret measurements in behavioral experiments.

With available technology, we have yet to address the diversity of chemical neurotransmission at scales crucial to understanding brain circuit function. Therefore the overarching goal of this UM1 proposal is to establish a multidisciplinary, multi-investigator, and multi-institution program focusing on developing tools for measuring molecular inputs to neurons and resulting activity, including: engineering optimized and multi-color FP-based indicators for NT/NM and voltage (Aim 1); detailed characterization and benchmarking of indicators in vivo (Aim 2); disseminating vetted, best-of-class reagents and related testing data (Aim 3).

Our effort will provide the foundation for unraveling the logic of input-output transformation in defined cell types in vivo, which underlie information processing, brain states, circuit plasticity, and (ultimately) behavior.

MAX Planck Florida

THE MISSION OF THE NATIONAL INSTITUTE OF MENTAL HEALTH (NIMH) IS TO TRANSFORM THE UNDERSTANDING AND TREATMENT OF MENTAL ILLNESSES THROUGH BASIC AND CLINICAL RESEARCH, PAVING THE WAY FOR PREVENTION, RECOVERY, AND CURE. WE FULFILL THIS MISSION BY SUPPORTING AND CONDUCTING RESEARCH ON MENTAL ILLNESSES, HEALTH SERVICES, AND THE UNDERLYING BASIC SCIENCE OF THE BRAIN AND BEHAVIOR; SUPPORTING THE TRAINING OF SCIENTISTS TO CARRY OUT BASIC AND CLINICAL MENTAL HEALTH RESEARCH; AND COMMUNICATING WITH SCIENTISTS, PATIENTS, PROVIDERS, AND THE PUBLIC ABOUT MENTAL HEALTH RESEARCH ADVANCES AND PRIORITIES. IN MAY 2024, NIMH RELEASED ITS STRATEGIC PLAN FOR RESEARCH. THE STRATEGIC PLAN BUILDS ON THE SUCCESSES OF PREVIOUS NIMH STRATEGIC PLANS BY PROVIDING A FRAMEWORK FOR SCIENTIFIC RESEARCH AND EXPLORATION, AND ADDRESSING NEW CHALLENGES IN MENTAL HEALTH.THE NEW STRATEGIC PLAN OUTLINES FOUR HIGH-LEVEL GOALS: GOAL 1: DEFINE THE BRAIN MECHANISMS UNDERLYING COMPLEX BEHAVIORS GOAL 2: EXAMINE MENTAL ILLNESS TRAJECTORIES ACROSS THE LIFESPAN GOAL 3: STRIVE FOR PREVENTION AND CURES GOAL 4: STRENGTHEN THE PUBLIC HEALTH IMPACT OF NIMH-SUPPORTED RESEARCH THESE FOUR GOALS FORM A BROAD ROADMAP FOR THE INSTITUTES RESEARCH PRIORITIES OVER THE NEXT FIVE YEARS, BEGINNING WITH THE FUNDAMENTAL SCIENCE OF THE BRAIN AND BEHAVIOR, AND EXTENDING THROUGH EVIDENCE-BASED SERVICES THAT IMPROVE PUBLIC HEALTH OUTCOMES.

93.242 - Mental Health Research Grants

National Institute of Mental Health (NIMH) [HHS - NIH]

Jupiter, Florida 334585293 United States

Single Zip Code

BRAIN Initiative: Engineering and optimization of molecular technologies for functional dissection of neural circuits (UM1 Clinical Trial Not Allowed) (RFA-MH-22-245)

Amendment Since initial award the total obligations have increased 167% from $2,359,031 to $6,304,282.