Robinson, Jacob2021-05-032021-11-012021-052021-04-30May 2021Sebesta, Charles. "Optimization of Fast Multiplexed Magnetogenetics." (2021) Diss., Rice University. <a href="https://hdl.handle.net/1911/110398">https://hdl.handle.net/1911/110398</a>.https://hdl.handle.net/1911/110398Precisely 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.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.MagnetogeneticsAlternating Magnetic fieldNanoparticlesNeuroengineeringMolecular BiologyDrosophilaTRPA1Thermally sensitive ion channelsNeuroscienceThesis2021-05-03