biostudies-literatureUnda SRNINDS NIH HHSNIH HHSeadp9150https://www.ebi.ac.uk/biostudies/studies/S-EPMC11463271biostudies-literatureUnknown10(41)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 Science advancesBidirectional regulation of motor circuits using magnetogenetic gene therapy.PMC11463271OT2 OD024912R01 NS097184Hassanzadeh GSchaffer CVaisey GDyke JPNishimura NFung EKAntoniazzi AMMolina HGrosenick LZirkel RWang PListon CMMarongiu RKaplitt MGNorman SKelly LPomeranz LEFriedman JMUnda SRYu XStanley SAfalseBidirectional 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 2024-01-01T00:00:00Z2024 Oct2025-04-04T08:18:10.817Z2025-04-04T08:18:10.817ZS-EPMC114632713938323010.1126/sciadv.adp9150