Publication Type Academic Article
Authors Unda S, Pomeranz L, Marongiu R, Yu X, Kelly L, Hassanzadeh G, Molina H, Vaisey G, Wang P, Dyke J, Fung E, Grosenick L, Zirkel R, Antoniazzi A, Norman S, Liston C, Schaffer C, Nishimura N, Stanley S, Friedman J, Kaplitt M
Journal Sci Adv
Volume 10
Issue 41
Pagination eadp9150
Date Published 10/09/2024
ISSN 2375-2548
Keywords Genetic Therapy, Dependovirus
Abstract 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.
DOI 10.1126/sciadv.adp9150
PubMed ID 39383230
PubMed Central ID PMC11463271
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