Over the past century, researchers have made incredible progress in understanding the anatomy, cell biology, physiology, and chemistry of the brain. Yet fundamental mysteries remain, such as how neural activity translates into behavior and why brain function declines with age. Diseases and disorders of the brain and nervous system represent some of the greatest challenges to modern medicine, and it is imperative that we develop effective ways of preventing and treating these devastating conditions. Recent advances in neuroimaging, genomics, computational neuroscience, engineering, and other disciplines have ushered in a new great era in neuroscience, during which we can expect to make transformative discoveries regarding brain function in health, aging and disease.
The NIH Blueprint for Neuroscience Research (Blueprint) aims to accelerate these discoveries. Blueprint, a collaboration among 15 participating NIH Institutes, Centers and Offices (ICs) that supports research on the nervous system, seeks to enhance cooperative activities and to accelerate the pace of discovery and understanding in neuroscience research. Blueprint was initiated in 2004 by the NIH Director (Dr. Elias Zerhouni), based on the premise that, by pooling resources and expertise, Blueprint ICs can take advantage of economies of scale, confront challenges too large for any single IC, and develop research tools and infrastructure that will serve the entire neuroscience community.
Looking forward to the next 10 years, the 15 participating NIH ICs that support Blueprint published a Request for Information (RFI) to seek input from the scientific community on how the Blueprint might best continue to support research on the brain and nervous system. Responses to the RFI are encouraged to suggest how future Blueprint investments can have a broad impact on neuroscience, and to identify research that has the potential to transform our basic understanding of the brain and our approaches to treating disorders.
The following are select highlights of previous Blueprint activities:
Blueprint Grand Challenges
Blueprint initiatives and programs have supported the development of new tools, training opportunities, and other resources to assist neuroscientists. In 2009, the Blueprint Grand Challenges were launched to catalyze research with the potential to transform our basic understanding of the brain and our approaches to treating disorders.
- The Human Connectome Project uses state-of-the-art neuroimaging technology to explore the connections within the human brain. This project is expected to greatly advance the capabilities for imaging and analyzing brain connections, resulting in improved sensitivity, resolution, and utility, thereby accelerating progress in the emerging field of human connectomics. It is expected to help answer questions about how genes influence brain connectivity, and, in turn, how this relates to mood, personality, and behavior. Participating investigators will collect brain imaging data plus genetic and behavioral data from 1,200 adults 22-35 years old. Building on the success of this project, in 2014 Blueprint authorized funds to expand the age range of normal subjects to include both younger individuals and adults over 35.
- The Grand Challenge on Chronic Pain seeks to shed light on the molecular, cellular and circuit-level changes underlying the transition from acute to chronic pain. Another aim of the initiative is to bring researchers from the neuroplasticity field into the pain field, and to train new investigators in state-of-the-art methods for studying pain. Mechanisms of research support include grants focused on understanding the maladaptive neurobiological changes that occur during the transition from acute to neuropathic pain. Additionally, investigators submit competitive revisions that propose a collaborative, one year pilot study or a new specific aim associated with an active NIH grant.
- The Blueprint Neurotherapeutics Network serves as a pipeline to move candidate drugs for neurological disorders through preclinical development into early clinical trials. The Network helps small labs develop new drugs for nervous system disorders by providing research funding, plus access to millions of dollars worth of services and expertise, to assist in every step of the drug development process – from laboratory studies to preparation for clinical trials. Project teams across the country have received funding to pursue drugs for conditions from vision loss to neurodegenerative disease to depression.
From 2007-2009, Blueprint focused on three major themes in neuroscience: neurodegeneration, neurodevelopment, and neuroplasticity. These efforts enable unique funding opportunities and training programs, and helped establish new resources and tools that continue to be available to researchers and the general public today. Some examples of resources developed through Blueprint include:
- The Neuroscience Information Framework (NIF) is an online portal, data sharing platform, and customized search engine for neuroscience-related data, tools, literature and websites. With more than 4,500 curated resources and direct access to more than 100 databases, NIF represents the largest source of neuroscience information on the web. Further, NIF offers a set of tools and best practices for sharing research data and resources.
- The Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) , an online bank of software and other tools used for neuroimaging. Users can search for tools on the site, upload tools, and exchange reviews. NITRC serves as a hub for finding a variety of neuroimaging tools, and an online community for getting technical information and assistance. NITRC users can quickly search for software tools used to support imaging methods for MRI, CT, PET/SPECT, EEG/MEG, and optical imaging. It also offers a cloud-based computing environment to help researchers manage and analyze large volumes of brain imaging data.
Gene Expression Databases:
- The Gene Expression Nervous System Atlas (GENSAT) and the Cre Driver Network are projects to create transgenic mouse lines expressing green fluorescent protein (GFP) reporters or DNA recombinases in specific neural and glial populations. In each mouse line, expression of the reporter or recombinase is controlled by promoter elements derived from a bacterial artificial chromosome (BAC) containing a specific gene of interest, in order to mimic expression patterns of genes. To date, over 160 fully characterized BAC-Cre lines have been created and are available from the Cre driver network and over 1400 (GFP and Cre) lines are available from GENSAT.
- The Blueprint Non-Human Primate Atlas is an online database of gene expression in the rhesus macaque brain from birth to four years old. The Atlas consists of a suite of gene expression data, neuroanatomical data, and informatics tools for exploring the cellular and molecular architecture of the developing rhesus macaque brain. Publicly accessible, the Atlas allows users to search for gene expression data by gene, brain region, and age. The Atlas is expected to aid research on human brain development and developmental disorders.
Clinical Research Tools:
The NIH Toolbox for Assessment of Neurological and Behavioral Function is a set of integrated tools for measuring neurologic and behavioral function, and for generating data that can be used and compared across diverse clinical studies. A multidimensional set of brief measures assessing cognitive, emotional, motor, and sensory function from ages 3 to 85, the Toolbox meets the need for a standard set of measures that can be used as a “common currency” across diverse study designs and settings.
Training and Education:
- Blueprint Training Programs help undergraduate and graduate students pursue interdisciplinary careers in neuroscience. Previous programs have focused on training in translational research and the neurobiology of disease. Current programs focus on computational neuroscience and brain imaging.
- The NIH Blueprint Enhancing Neuroscience Diversity through Undergraduate Research Experiences (ENDURE) supports undergraduates from underrepresented groups in a two-year neuroscience research program and encourages matriculation into PhD programs.
- Blueprint funds efforts to develop new approaches to teaching neuroscience through K-12 instruction and through less traditional means, such as museum exhibits and web-based platforms.
The next iteration of Blueprint should have a transformative impact by paving the way toward a detailed understanding of how our brain circuitry changes as we age, and how it differs in psychiatric and neurologic illness.
What should the next Blueprint Grand Challenge be? What major opportunities and impediments to advancing neuroscience research are not currently being addressed? How should we train the next generation of neuroscientists? How can we increase diversity in the neuroscience workforce? What major neuroethics challenges need to be addressed? If you have thoughts on any of these topics, particularly related to the Blueprint RFI, follow this link to submit your input.
As always, we also appreciate general thoughts and comments related to the previous Blueprint efforts mentioned in this blog post in the comments section below.