Optimization of Fast Multiplexed Magnetogenetics

Date
2021-04-30
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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.

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Degree
Doctor of Philosophy
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Thesis
Keywords
Magnetogenetics, Alternating Magnetic field, Nanoparticles, Neuroengineering, Molecular Biology, Drosophila, TRPA1, Thermally sensitive ion channels, Neuroscience
Citation

Sebesta, Charles. "Optimization of Fast Multiplexed Magnetogenetics." (2021) Diss., Rice University. https://hdl.handle.net/1911/110398.

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