| First Author | Unda SR | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 41 | Pages | eadp9150 |
| PubMed ID | 39383230 | Mgi Jnum | J:355218 |
| Mgi Id | MGI:7738104 | Doi | 10.1126/sciadv.adp9150 |
| Citation | Unda SR, et al. (2024) Bidirectional regulation of motor circuits using magnetogenetic gene therapy. Sci Adv 10(41):eadp9150 |
| abstractText | 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 c-fos 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. |
