Bidirectional Regulation of Motor Circuits Using Magnetogenetic Gene Therapy
DOI10.5281/zenodo.12761093Zenodo12761093MaRDI QIDQ6724669FDOQ6724669
Dataset published at Zenodo repository.
Santiago Unda, Gholamreza Hassanzadeh, Edward Fung, George Vaisey, Roberta Marongiu, Conor Liston, Lisa Pomeranz, Sarah Stanley, Aldana Antoniazzi, Henrik Molina, Leah Kelly, Nozomi Nishimura, Chris B. Schaffer, Jonathan Dyke, Rick Zirkel, Putianqi Wang, Jeffrey Friedman, Michael Kaplitt, Sofya Norman, Logan Grosenick, Xiaofei Yu
Publication date: 17 July 2024
Copyright license: Creative Commons Attribution 4.0 International
Here we report a novel suite of magnetogenetic tools, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. AAV-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine 2a receptor-cre driver mice resulted in motor freezing when placed in an MRI or adjacent to a transcranial magnetic stimulation (TMS) device. Functional imaging and fiber photometry both confirmed activation of the target region in response to the magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing cre into the globus pallidus led to similar circuit specificity and motor responses. Finally, a mutation was generatedto gate chloride and inhibit neuronal activity. Expression of this variant in subthalamic nucleus in PitX2-cre parkinsonian mice resulted in reduced local c-fos expression and motor rotational behavior.These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits non-invasivelyin-vivousing clinically available devices.
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