The BRAIN Initiative: developing technology to catalyse neuroscience discovery

Abstract

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.

Keywords: BRAIN Initiative; neural circuitry; neurotechnology.

Figure 1.

Not Cajal's microscope. Photograph of a current, state of the art, light sheet microscopy system. Image courtesy of Mr Matt Staley and Dr Phillipp Keller, Howard Hughes Medical Institute Janelia Research Campus.

Figure 2.

Integrating neuroscience and chemical engineering—CLARITY technique. Images courtesy of the Deisseroth Laboratory, Stanford University. (a) Mouse brain prior to CLARITY transformation (left). Following CLARITY, the brain is rendered transparent while preserving its structural integrity (right). (b) High-resolution fluorescence signals (as well as antibody labels and oligonucleotide probes) pass entirely through intact brains in CLARITY (shown is an adult mouse brain with long-range projections labelled in green with a genetic marker).

Figure 3.

Spatial scales of structural analysis. (a) Macro-connectomics. Diffusion-weighted magnetic resonance imaging (DW MRI) with approximately millimetre spatial resolution (voxel volume 1 × 1 × 1 mm cubed) enables non-invasive mapping of long distance tracts within the entire human brain, which can then be related to functionally defined regions in functional magnetic resonance imaging (fMRI) experiments in the same spatial scale, as in (b). (c) Meso-connectomic approaches are capable of mapping both local and interarea connectivity at cellular resolution (micrometre spatial scale). (d) Dense electron microscopic reconstruction with nanometre in-plane resolution and serial slices of 50–100 nm enables micro-connectomic mapping of circuitry at the level of individual cells and synapses. Relating these three levels of structural analysis to each other and to data streams from genetic, electrophysiological, optical, perturbation, behavioural, etc. experiments is a central challenge of the BRAIN Initiative. (a, b and d) Courtesy of Dr Kamil Ugurbil, University of Minnesota ((a) from [59], (b) generated from the Washinton University, University of Minnesota Human Connectome Project data by Saad Jbabdi, Oxford University; (d) from supplemental data supplied in [60]). (c) Courtesy of Dr Joshua Sanes, Harvard University, and Dr Dawen Cai, University of Michigan.