Bidirectional regulation of motor circuits using magnetogenetic gene therapy
Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to 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. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced <i>c-fos</i> expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.
Authors
- Roberta Marongiu (ORCID: https://orcid.org/0000-0002-7609-7000)
- Santiago R. Unda (ORCID: https://orcid.org/0000-0001-7319-6794)
- Aldana M. Antoniazzi (ORCID: https://orcid.org/0000-0002-0728-3352)
- Jonathan P. Dyke (ORCID: https://orcid.org/0000-0001-7170-488X)
- Edward K. Fung (ORCID: https://orcid.org/0000-0002-3390-1548)
- Henrik Molina (ORCID: https://orcid.org/0000-0001-8950-4990)
- Sofya Norman (ORCID: https://orcid.org/0000-0002-1665-6501)
- Michael G. Kaplitt (ORCID: https://orcid.org/0000-0002-8979-2459)
- George Vaisey (ORCID: https://orcid.org/0000-0002-8359-1314)
- Conor Liston (ORCID: https://orcid.org/0000-0002-1639-5401)
- Nozomi Nishimura (ORCID: https://orcid.org/0000-0003-4342-9416)
- Logan Grosenick (ORCID: https://orcid.org/0000-0003-3216-0319)
- Xiaofei Yu (ORCID: https://orcid.org/0000-0002-1712-331X)
- Jeffrey M. Friedman (ORCID: https://orcid.org/0000-0003-2152-0868)
- Chris B. Schaffer (ORCID: https://orcid.org/0000-0002-7800-9596)
- Leah Kelly
- Sarah A. Stanley (ORCID: https://orcid.org/0000-0002-0253-2663)
- Lisa E. Pomeranz (ORCID: https://orcid.org/0000-0002-8117-7355)
- Putianqi Wang
- Rick Zirkel (ORCID: https://orcid.org/0000-0003-1744-0785)
- Gholamreza Hassanzadeh (ORCID: https://orcid.org/0000-0002-5213-1630)
Institutions
- Allen Institute for Brain Science (US)
- Howard Hughes Medical Institute (US)
- Vrije Universiteit Brussel (BE)
- Citigroup (US)
- Cornell University (US)
- Fudan University (CN)
- Rockefeller University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science Advances
- Published
- 2024-10-09
- DOI
- https://doi.org/10.1126/sciadv.adp9150
- Citations
- 14
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 3.76