CAREER: Chemical Tools for Bio-Orthogonal Neuromodulation

With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Rachel Steinhardt of Syracuse University will develop chemical tools to understand how individual cells communicate to create brain activity. Decoding this communication promises to enable new insights into phenomena such as learning, mood, and sleep. The research focuses on the chemical synthesis of probes and optimization of their chemical and biochemical properties. They will then be tested in assays that determine the ability of the probe to interact with a target in a spatially- or temporally defined manner, which can then be correlated to a biochemical or neuronal event. The interdisciplinary nature of this program will allow graduate students and undergraduates to gain expertise in modern research techniques. The project also integrates an outreach program to teach chemistry in an after school program at middle schools Syracuse City School District. One of the most perplexing challenges in neuroscience is how to explain the brain’s ability to learn and change itself, creating seemingly infinite behaviors and states (sleeping, wakefulness, attention) while using a fixed anatomical connectivity. To answer these questions, it is necessary to define the link between membrane-bound receptor binding events and the ensemble activity of neurons. Unfortunately, there is a paucity of chemical tools to adequately probe neural activity via stimulation of the native receptors. The Steinhardt lab will address this need by synthesizing probes for spatially defined native receptor control and temporally defined neurochemical signaling,that will then be used in biochemical and primary cell-based assays. These probes are small molecule methods for researchers to control native chemical synapses with light. Such probes are expected to facilitate bottom-up experiments (i.e., cell to neural network) to determine the mechanistic relationship between learning and neural state flexibility and modulation of native dopamine and serotonin receptor subtypes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.