Optimization of Fast Multiplexed Magnetogenetics
Date
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here I demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Additionally, I have identified novel TRPA1 channels that show promise of translating this work into mammalian systems. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, I can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.
Description
Advisor
Degree
Type
Keywords
Citation
Sebesta, Charles. "Optimization of Fast Multiplexed Magnetogenetics." (2021) Diss., Rice University. https://hdl.handle.net/1911/110398.