The centers will be created through a new notice of funding opportunity (NOFO) that is part of a family of NOFOs supporting the BRAIN Initiative Armamentarium transformative project. This NOFO is anticipated to be published in December 2022 with an expected application due date in June 2023 and an earliest start date in April 2024
Molecular tools that report neural states (e.g., membrane voltage, intracellular calcium, etc.) or alter neural states (e.g., optogenetics, chemogenetics etc.) have become indispensable for revealing how neural circuits work, and to establish causal relationships between neural activity and behavior. A promise of these molecules is that they can be used to probe activity of individual cells and even individual synapses across tens of thousands of neurons. But robust and reliable application of these technologies across species requires further optimization of current tools. Improvements are needed to expand the scope of brain cell monitoring and manipulation capabilities. Optimization will involve molecular engineering, in vivo validation of improvements in performance, benchmarking against best-in-class tools, and the adaptation of tools for easy use by neuroscientists.
This Notice (NOT-MH-22-265) outlines a new NOFO that will use the UM1 cooperative agreement activity code to support the creation of Molecular Payloads Centers. These Centers will accelerate the design and optimization of high-impact molecular tools that can be delivered selectively as payloads to distinct cell types for monitoring and/or manipulating brain cell activity in experimental animals. The new NOFO will join a family of NOFOs (including RFA-MH-20-556 and RFA-MH-21-180) under the BRAIN Initiative Armamentarium transformative project, whose goal is to generate tools to specifically access, manipulate and monitor cell types in the nervous system in multiple species.
The purpose of this Notice (NOT-MH-22-265) is to allow potential applicants sufficient time to develop the appropriate collaborations for responsive projects. More details of the Notice can be found here.
Background
Until recently, the detailed cellular make-up of the brain, critical for understanding how the brain works, has remained a mystery. While neuroscientists appreciated that there would be some diversity of brain cell-types, the application of genomic technologies in the last two decades have revealed a rich catalog of cell-types far beyond what most neuroscientists might have expected. Led in part by collaborative BRAIN Initiative projects such as the BRAIN Initiative Cell Census Consortium, and subsequently the BRAIN Initiative Cell Census Network (BICCN), research efforts most recently culminated in the detailed cataloging of major cell types in a part of the brain that controls movement in mice, non-human primates, and humans. However, the function of these diverse cell types remains to be discovered.
In a parallel undertaking over the last few decades, neuroscientists, physicists, and engineers have also invested substantial time and effort in the development of new molecular tools to study large swaths of the brain in action, and to artificially tinker with patterns of brain activity. Such tools serve the dual role of revealing the beautiful symphony of neural activity in the healthy brain but also the cacophony that ensues when specific instruments are silenced or play out of turn in an orchestra.
The convergence of detailed cataloging of brain cell-types and molecular technologies to dissect neural function now presents an opportunity to tease apart the functional roles of distinct elements of the neural symphony in brain function. Indeed, the development of an armamentarium of tools for precise cell access in the brain is one of three transformative projects launched by the NIH BRAIN Initiative as outlined in a recent commentary by NIH BRAIN Initiative director Dr. John Ngai. The maturation of early investments of the BRAIN Initiative into new scientific directions holds the promise of revolutionizing our understanding of the brain, and for precision tools to help those suffering from neurological disease.