title: Genetically targeted magnetic control of the nervous system.
abstract: Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several limitations, including invasive modes of stimulation or slow on/off kinetics. We have overcome these disadvantages by synthesizing a single-component, magnetically sensitive actuator, "Magneto," comprising the cation channel TRPV4 fused to the paramagnetic protein ferritin. We validated noninvasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, we used Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together our results present Magneto as an actuator capable of remotely controlling circuits associated with complex animal behaviors.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.|Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Michael A
authors.identifier: http://orcid.org/0000-0002-0689-6384
authors.initials: MA
authors.lastname: Wheeler
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Smith
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ottolini
authors.affiliation: Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, USA.|Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Barker
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Aarti M
authors.initials: AM
authors.lastname: Purohit
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Grippo
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Gaykema
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Spano
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Beenhakker
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.|Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kucenas
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Patel
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.|Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.|Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Deppmann
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ali D
authors.initials: AD
authors.lastname: Güler
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology; D005293:Ferritins / Q000235:genetics; D006801:Humans; D008280:Magnetics / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012201:Reward; D050916:TRPV Cation Channels / Q000235:genetics; D015027:Zebrafish
chemical_list: D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D005293:Ferritins