▶︎ CANCELED: Frontiers in Chemical Biology Seminar

Molecular insights play an essential role in biology and physiology. However, for the information-processing functions of the brain, the impact of molecular thinking has been limited. This is largely due to challenges with measuring neuron activity and molecular information from the same cells. To solve this problem, we developed Calcium and RNA Multiplexed Activity (CaRMA) imaging based on recording in vivo single-neuron calcium dynamics deep in the mouse brain followed by gene expression analysis in the same cells. Our findings quantitatively demonstrate that molecularly defined neurons are important information processing units for brain function. Because of the importance of cell types in brain function, we have also focused on developing chemogenetic ion channels with sub-nM potency agonists that are highly effective in rodents and a nonhuman primate. These tools can be used for research purposes with our novel, high selectivity synthetic agonists and potentially clinical applications with an FDA-approved drug. These chemistry-based platforms offer an opportunity to advance understanding of the brain as an organ and an information processing system, which is essential to find treatments for challenging pharmacotherapy-resistant neurological and psychiatric diseases.