RF1MH128875

A 3D Multimodal Micron-Scale Human Brain Atlas Bridging Single Cell Data, Neuropathology and Neuroradiology - Digitized Reference Brains, also referred to as Common Coordinate Frameworks (CCFs), together with superposed atlas annotations, are of central importance to neuroscience. They bear the same relation to neuroscience as do reference genomes and genome annotations to cellular and molecular biology. Strikingly, however, such reference brains for humans lag far behind the corresponding CCFs for non-human model organisms such as the laboratory mouse. Existing data sets either have sections spaced relatively far apart or lack in-plane resolution down to the micron scale. Crucially, existing data sets are not well connected to the major areas in medicine that deal with the human brain, namely neuroradiology and neuropathology. We will meet this need by creating an unprecedented micron-scale, 3D atlas that combines multiple MRI modalities as well as continuous serial section histology. In particular, the reference atlas will consist of Nissl, myelin and H&E stains, with 20 micron contiguous serial sections, and approximately ~8000 sections/brain. We will do so using the tape-transfer method, which preserves tissue geometry even in the presence of disconnected pieces to the brain being sectioned, and permits 3D reassembly of the sections into a 3D volume. We will utilize diffeomorphic mapping methods to co-register the MRI and histological data, and will create a human brain CCF in which single-cell transcriptomic and epigenomic data can be pinned in order to create a human brain cell atlas. We will use machine learning approaches to segment cells and processes in these images and to algorithmically detect cytoarchitectonic boundaries; such machine learning methods will also be used to predict histology and cytoarchitecture from MRI data, with our collected data as a training set. We will make our data freely available to scientists as well as medical professionals through an online data portal with a multi-resolution viewer for zooming and panning through terapixel image data, and also deposit the data in a shared data repository to make it easily accessible to other researchers. We will connect our data to a unique on-line neuropathology resource containing over a petabyte of neuropathological images, including H&E stained sections from the coronal plane. We expect that the reference brain data we produce will become the de-facto standard for a high-resolution reference atlas for the human brain.

Cold Spring Harbor Laboratory

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. IN MAY 2020, NIMH RELEASED ITS NEW STRATEGIC PLAN FOR RESEARCH. THE NEW 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 INSTITUTE'S 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. THE INSTITUTE'S OVERALL FUNDING STRATEGY IS TO SUPPORT A BROAD SPECTRUM OF INVESTIGATOR-INITIATED RESEARCH IN FUNDAMENTAL SCIENCE, WITH INCREASING USE OF INSTITUTE-SOLICITED INITIATIVES FOR APPLIED RESEARCH WHERE PUBLIC HEALTH IMPACT IS A SHORT-TERM MEASURE OF SUCCESS. THE NEW STRATEGIC PLAN ALSO ADDRESSES A NUMBER OF CROSS-CUTTING THEMES THAT ARE RELEVANT TO ALL RESEARCH SUPPORTED BY NIMH, THESE THEMES HIGHLIGHT AREAS WHERE NIMH-FUNDED SCIENCE MAY HAVE THE GREATEST IMPACT, BRIDGE GAPS, AND OFFER NOVEL APPROACHES TO ACCELERATE ADVANCES IN MENTAL HEALTH RESEARCH. FOR EXAMPLE, NIMH VALUES A COMPREHENSIVE RESEARCH AGENDA THAT TAKES AN INCLUSIVE APPROACH THAT ENSURES RESEARCH INTERESTS ARE VARIED, MAINTAIN DIVERSE PARTICIPATION AND PARTNERSHIPS, AND ACHIEVE RESEARCH GOALS ACROSS MULTIPLE TIMEFRAMES. THIS INCLUDES DIVERSE METHODOLOGIES, TOOLS, AND MODELS, RESEARCH ADDRESSING COMPLEX BASIC, TRANSLATIONAL, AND APPLIED QUESTIONS, RESEARCH INCLUDING BOTH SEXES AND, AS APPROPRIATE, GENETIC BACKGROUND, AND, PARTICIPANTS FROM DIVERSE RACIAL AND ETHNIC BACKGROUNDS, AND ACROSS GENDER IDENTITIES, GEOGRAPHICAL CONTEXT, SOCIOECONOMIC STATUS, NEUROTYPE, AND AGE OFFERING THE BEST POSSIBLE REPRESENTATION, FOR THE BROADEST NUMBER OF INDIVIDUALS WHO MAY ULTIMATELY BENEFIT FROM THESE SCIENTIFIC ADVANCES. TO ACCOMPLISH THE GOALS OUTLINED IN THE NEW STRATEGIC PLAN, NIMH WILL SUPPORT RESEARCH THAT AIMS: TO CHARACTERIZE THE GENOMIC, MOLECULAR, CELLULAR, AND CIRCUIT COMPONENTS CONTRIBUTING TO BRAIN ORGANIZATION AND FUNCTION, TO IDENTIFY THE DEVELOPMENTAL, FUNCTIONAL, AND REGULATORY MECHANISMS RELEVANT TO COGNITIVE, AFFECTIVE, AND SOCIAL DOMAINS, ACROSS UNITS OF ANALYSIS, AND, TO GENERATE AND VALIDATE NOVEL TOOLS, TECHNIQUES, AND MEASURES TO QUANTIFY CHANGES IN THE ACTIVITY OF MOLECULES, CELLS, CIRCUITS, AND CONNECTOMES. TO DISCOVER GENE VARIANTS AND OTHER GENOMIC ELEMENTS THAT CONTRIBUTE TO THE DEVELOPMENT OF MENTAL ILLNESSES IN DIVERSE POPULATIONS, TO ADVANCE OUR

93.242 - Mental Health Research Grants

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

Cold Spring Harbor, New York 117242209 United States

Single Zip Code

BRAIN Initiative Cell Census Network (BICCN) Scalable Technologies and Tools for Brain Cell Census (R01 Clinical Trial Not Allowed) (RFA-MH-21-140)

Amendment Since initial award the End Date has been extended from 08/31/24 to 08/31/25.