Next Generation Magnetogenetic Tools for Manipulating Neural Activity

2016 Seed Grant
Ali Guler, Ph.D.
University of Virginia

One of the fundamental scientific challenges of our time is to understand how the brain works. To achieve this, we must precisely manipulate neurons to observe resultant physiological or behavioral responses. The “dream tool” for neural circuit control would be one that remotely manipulates specific cells with temporal resolution approaching endogenous neuronal activity rates. In this proposal, I outline a strategy to engineer magnetically-controlled ion channels, receptors, and genome editors that can fulfill this dream. In contrast to current methods for circuit control, this approach will be minimally invasive while operating at physiologically relevant speeds and allowing manipulation of defined subsets of neurons. In addition to its uses in basic neuroscience research, the magnetogenetic toolset will be adaptable to the rescue of ill-firing neural networks or erroneous transcriptional activity to remediate brain diseases.