Bidirectional Regulation of Motor Circuits Using Magnetogenetic Gene Therapy Short: Magnetogenetic Regulation of Motor Circuits.

Autor:	Unda SR; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, Cornell University; New York, NY, USA., Pomeranz LE; Laboratory of Molecular Genetics, Rockefeller University; New York, NY, USA., Marongiu R; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, Cornell University; New York, NY, USA., Yu X; School of Life Sciences, Fudan University, Shanghai, 200433., Kelly L; Laboratory of Molecular Genetics, Rockefeller University; New York, NY, USA., Hassanzadeh G; VIB Nanobody Core, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels., Molina H; Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Vaisey G; Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, NY 10065, USA., Wang P; Laboratory of Molecular Genetics, Rockefeller University; New York, NY, USA., Dyke JP; Citigroup Bioimaging Center, Weill Cornell Medical College, Cornell University; New York, NY, USA., Fung EK; Citigroup Bioimaging Center, Weill Cornell Medical College, Cornell University; New York, NY, USA., Grosenick L; Department of Psychiatry, Weill Cornell Medical College, Cornell University; New York, NY, USA., Zirkel R; Meining School of Biomedical Engineering, Cornell University, Ithaca, NY, USA., Antoniazzi AM; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, Cornell University; New York, NY, USA., Norman S; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, Cornell University; New York, NY, USA., Liston CM; Department of Psychiatry, Weill Cornell Medical College, Cornell University; New York, NY, USA., Schaffer C; Meining School of Biomedical Engineering, Cornell University, Ithaca, NY, USA., Nishimura N; Meining School of Biomedical Engineering, Cornell University, Ithaca, NY, USA., Stanley SA; Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Friedman JM; Laboratory of Molecular Genetics, Rockefeller University; New York, NY, USA., Kaplitt MG; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, Cornell University; New York, NY, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 29. Date of Electronic Publication: 2024 Apr 29.
DOI:	10.1101/2023.07.13.548699
Abstrakt:	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 generated to 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-invasively in-vivo using clinically available devices. Competing Interests: Competing interest The authors declare no competing interests.
Databáze:	MEDLINE
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