Project 1 – Optical dissection of neural activity during naturalistic behavior and diseased states
My laboratory develops, disseminates, and uses multi-color, genetically encoded indicators that sense released neurotransmitters, neuromodulators, and neuropeptides. We aim to understand the complex interactions of released neurochemicals on neural activity. Using a novel high-throughput sensor engineering platform, including ligand-binding scaffolds, computational modeling, and machine learning-guided directed evolution, we create highly optimized sensors covering the full-color spectrum with enhanced chemical specificity, resolution, and depth across biological systems.
Biosensors permit chronic, direct, and precise measurements of the spatiotemporal dynamics of neurochemical release during a behavioral task. Moreover, these measurements can be combined with modern optical approaches and electrical recordings to measure and manipulate additional circuit components.
To ensure that our efforts have maximum impact, we form interdisciplinary collaborations to benchmark and cross-validate these tools in various model systems, followed by broad dissemination of our technology to end users before and after publication. We strongly believe in the open sharing of our technologies to accelerate the development of new and refined theories of neuromodulation. Published reagents are disseminated through viral cores, including UNC NeuroTools, Addgene, and the Neurophotonics platform.
In addition to sensor engineering, we apply our biotechnologies to visualize neuromodulator and peptide release dynamics across cortical and subcortical regions during naturalistic behaviors. We can achieve sub-second synchrony between brain activity recordings and behavior by using machine learning to detect precise movement epochs. A significant aspect of our research involves studying how stress impacts neurotransmitter release patterns in the brain—an essential consideration given stress’s ubiquitous presence and substantial role as a risk factor for conditions like anxiety and depression. Specifically, we are interested in how alterations in brain neurotransmitter dynamics lead to stress-induced changes in behavior (Link). Understanding how stress modifies neurotransmitter release offers deeper insights into the effects of stress on brain function and its implications for related disorders.