BRAIN EAGER: Electrogenetic Reporters of Neural Activity

University Of Utah, Salt Lake City UT

Investigators

Abstract

Genetically-encoded reporters of neural activity are a transformative tool for understanding brain function because they allow for the simultaneous measurement of activity across many neurons defined by genetic and anatomical criteria. The current generation of such reporters use light to signal activity, which limits their ability to be used deep in brain tissue and across the full range of neuronal activity. The goals of the project are to overcome these limitations by developing reporter proteins that can be engineered to emit unique electrical or magnetic signals in response to neural activity. The project will also develop sensors that are optimized for detecting these signals from individual neurons in intact brain tissue in the freely-behaving animal. The proposed 'electrogenetic' toolbox will allow neural activity to be recorded with high fidelity from defined cell types across the entire physiological range of neuronal firing rates, from any location in the mammalian brain, and in the freely-behaving animal. This strategy leverages existing and widely available technology for recording electromagnetic signals in the brain, and thus has the potential to be rapidly adopted for a wide range of neuroscience applications. This project will develop a new strategy for measuring neural activity from genetically-targeted neurons in the intact brain. An interdisciplinary team of investigators will first use gene therapy techniques to express candidate proteins in particular neurons, then will screen for electrical or magnetic signals using conventional electrodes or nanoscale magnetometer probes. Understanding how neurons of a particular type are activated in the behaving animal is crucial for understanding the neural basis of sensation, cognition and behavior. Indeed, the lack of tools for interrogating identified neurons while they are in action is a major impediment to understanding functional neural circuits in the brain. In addition to breaking this impasse in basic science, a potential broader impact of this project is that the tools to be developed in this proposal may provide information leading to improved diagnosis and treatment of nervous system disorders including mental illness, autism, addiction and epilepsy.