University of California, Davis
In vivo proteomic labeling of functionally-defined neuronal circuits
Each of the ~86 billion neurons in the brain can be described by its connections, neural activity, and genetic makeup. Neuroscience has benefited from an explosion of recent technologies that allow us to trace individual connections between neurons; record the activity from neurons distributed across the brain; and sequence the RNA of thousands of cells. While mapping these properties in as many neurons and regions as possible is an incredible resource for the field, examining only one of these properties in isolation is not sufficient to create a holistic understanding of how the brain performs computation and regulates behavior.
Our laboratory aims to develop technologies that can capture a behaviorally relevant network of neurons, and 1) map their connections, 2) measure their gene or protein expression, and 3) perturb their function or signaling during animal behavior. To generate the most impactful technologies as possible, we test and apply these methods to a single focused question – how the brain regulates the powerful innate drive to seek reward. Understanding this behavior is incredibly important, because it is conserved across all species and is essential to species survival, including in the mouse animal model that we employ.
Our technologies, inspired by interdisciplinary approaches from synthetic biology and chemistry, are designed to reveal which molecular markers are enriched in neurons that play a critical role in suppressing reward-seeking behavior. Our studies could thus reveal cellular substrates for targeting these neurons in novel therapeutics to treat neuropsychiatric diseases. More broadly, the ability to functionally tag, manipulate, and molecularly probe behaviorally-relevant populations of neurons will be a transformative technology for the field of systems neuroscience – where we often lack the genetic tools to capture the appropriate neuronal subset that drives behavior.