What major BRAIN-funded scientific advancements or conversations has NIDA been a part of?
As one of the Institutes co-leading the BRAIN Initiative’s Tools and Technologies for Brain Cells and Circuits research program, NIDA has been closely involved in shaping and supporting the inventory and molecular mapping of cell classes across the whole mouse brain, and there are ongoing plans to accomplish the same in human and nonhuman primate brains.
A component of this program is the Cell Census Network, and among the brain regions of central interest in this project are the basal ganglia. The basal ganglia comprise the reward pathway and other circuits that play a major role in substance use disorders. Scientific staff at NIDA and several NIDA-funded grantees are participating in the effort to create a systematic map of this region to enhance our knowledge of its cellular and molecular architecture. This research could potentially lead to tools that could selectively target the basal ganglia’s cellular constituents, which would be a game changer for NIDA science.
Through BRAIN Initiative programs like BBQS mentioned above, NIDA has been co-leading discussions about advancing cause and effect relationships in human neuroscience research. We now have large neurocognitive datasets that can be mined and analyzed using large-scale network approaches, such as those generated by the Human Connectome Project and the ongoing ABCD study. These databases have enabled novel insights about fundamental brain function and neurocognitive dysfunction. For instance, ABCD is deepening our understanding of how environmental exposures affect neurocognition including revealing factors like economic disadvantage and social discrimination that can be targeted in prevention efforts. But while these datasets are excellent for identifying associations between network structure/function and behavior, they generally cannot help us establish causal relationships, leaving a gap in our ability to translate findings to clinical application.
Data derived from new methods and approaches like systematic circuit perturbation in combination with neural recordings in a behavioral context hold potential to fill this gap and significantly advance our understanding of these important cause and effect relationships in human neuroscience.
How has the BRAIN Initiative advanced or shaped NIDA’s mission?
Many tools developed through the BRAIN Initiative are helping NIDA scientists understand how drugs affect the brain, from cellular to circuit levels. For example, NIDA’s BRAIN-inspired research programs are already producing exciting findings. One of them is NIDA Single Cell Opioid Response in the Context of HIV, or SCORCH, which is applying single-cell sequencing-based approaches to inventory the cellular targets of drugs and the changes in those targets that drugs induce. A NIDA-funded team has recently identified a group of neurons in the dorsal peduncular nucleus, a brain region central to emotional regulation, reward, and motivation, that act as a master regulator of opioid reward.
Another NIDA initiative inspired by BRAIN is the Neural Ensembles and Used Substances (NExUS) Collaboratory, which seeks to integrate molecular information from cell taxonomies with measurement of neuronal population dynamics in behaving animals. NExUS aims to decipher how activity within the mosaic of brain cells “encode” particular properties of misused substances, such as the analgesic versus addictive properties of opioids. A NIDA-funded team has also recently used a mouse model to identify a brain circuit that mediates placebo pain relief.
In its 10 years, the BRAIN initiative has provided tools to visualize, monitor, and manipulate brain activity from molecular to network levels and has led to an exponential growth in understanding of how the brain functions. NIDA has been a key player in this effort, and our Institute continues to apply these new tools and emerging knowledge to inform research on urgent questions under its mission to advance the science of drug use and addiction.