Two Years Since the BRAIN Initiative: Update on Current Scientific and Technological Neuroscience Advancements.

On April 2, 2013, President Obama announced the commencement of the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, as part of a presidential focus on further understanding the human brain . Many neurosciences view this as a long-awaited relief, as funding rates for research grants reached an all-time nadir. The focus of the initiative was aimed at accelerating both the development and application of technology in the field of neuroscience, with an ultimate goal of providing new methods to diagnose, treat, and prevent neurologic disorders. The charge of the BRAIN Initiative, as summarized by National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D., is “to accelerate the development and application of innovative technologies to construct a dynamic picture of brain function that integrates neuronal and circuit activity over time and space .” One of the most substantial changes has been the announcement of dozens of leading technological firms, academic institutions, scientists, and other key contributors to the field of neuroscience, who have made commitments to advancing the initiative, with a 12-year research strategy for NIH to achieve the goals of the BRAIN Initiative . The gaps in knowledge that will be the target of the BRAIN Initiative include: “forming a comprehensive, rigorous inventory of different brain cell types, developing the technology to map circuits of the brain, improving methods for large-scale mapping of neural activity, developing and applying interventional tools that can change neural circuit dynamics to link brain activity to behavior, identifying new tools to understand the biological basis of mental processes, and finally discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception and action in health and disease .” Two years since the launch of the BRAIN Initiative, there has been some early progress in the development of novel technologies. Published in the May 2015 issue of Neuron, scientists have described a new method to turn behaviors both on and off in rodents. Using a technique known as DREADDs (designer receptors exclusively activated by designer drugs), Bryan Roth et al. were able to control neuronal circuitry and behavior in rodents , selectively turning them both on and off. This is in contrast to the field of optogenetics, which is a bulky, labor-intensive technique that allows scientists to label neurons with a light-sensitive protein (e.g., channelrhodopsin-2, then use pulses of light to turn genes on and off) . They developed a new DREADD (Designer Receptors Exclusively Activated by Designer Drugs) using the kopioid receptor (KOR), which is activated by the inert ligand SALB (salvinorin B), then expressed KORD in several neuronal contexts (including cells in the substantia nigra [SN], ventral tegmental area [VTA], arcuate nucleus [ARC], and paraventricular hypothalamus [PVH]) to selectively modify distinct neuronal populations and their respective circuits. By silencing via KORD of VTA/SN neurons, they were able to