In the Training Core, our central goal is education, outreach, and active support for rigorous and effective implementation of state-of-the-art circuit analysis tools, specifically in the setting of drug of abuse research. Here we expand upon the team?s existing training infrastructure, but move in new directions essential for the field-- specifically seeking to enable and advance the study of drug abuse and related phenomena with these methods, and assisting others seeking to learn and apply modern circuit analysis tools (focusing on optogenetics, ofMRI, CLARITY, and fiber photometry) to further this mission.
In Aim 1 we specifically leverage our infrastructure for advancing the application of modern optogenetic methods to drug abuse research, including in the setting of optogenetic functional MRI (ofMRI) readouts, multiunit electrophysiology readouts, and behavioral readouts in awake rodents. Trainees directly benefiting from the Core (with no charged cost or obligation) will include (across all categories and career stages) 1) P50 Center personnel; 2) all labs from the NIDA intramural research program (including but not limited to collaborative groups) and leading human brain banks; and 3) researchers across the nation and world with drug-abuse relevant basic or applied missions. Second, CLARITY is a technology for creating composites of biological molecules in tissue covalently linked to acrylamide-related polymer hydrogels, allowing removal of unlinked tissue elements to create transparency and accessibility to macromolecular labels; the resulting new structure allows high-resolution optical access to structural and molecular detail within intact tissues without disassembly.
In Aim 2 we specifically leverage our infrastructure for advancing the application of modern CLARITY to drug abuse research, targeting the participant categories above. And third, fiber photometry is a versatile method for collecting activity information from anatomically and/or genetically-defined cells and projections across the brain during free behavior, in a manner designed to be exactly aligned with optogenetic intervention via the same device and positioning in the same experimental subject.
In Aim 3, we specifically leverage our infrastructure for advancing the application of fiber photometry methods to drug abuse research, targeting the same participant categories with drug-abuse relevant vision. The Training Core, by disseminating versatile, powerful new circuit-dynamics tools for use in the NIDA Center and for the drug abuse community more broadly, will advance the understanding of drug altered states, of drug abuse and recovery, and of the brain itself as a dynamical system. This Core is tightly intertwined with the work in all 4 projects, but we will be alert to new opportunities for cross-fertilization certain to arise in the Center.
| Wang, Xiao; Allen, William E; Wright, Matthew A et al. (2018) Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science 361: |
| Lovett-Barron, Matthew; Andalman, Aaron S; Allen, William E et al. (2017) Ancestral Circuits for the Coordinated Modulation of Brain State. Cell 171:1411-1423.e17 |
