title: Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism.
abstract: Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP-TRPV1). Neuronal inhibition via the same stimuli is achieved by mutating the TRPV1 pore, rendering the channel chloride-permeable. These constructs were targeted to glucose-sensing neurons in the ventromedial hypothalamus in glucokinase-Cre mice, which express Cre in glucose-sensing neurons. Acute activation of glucose-sensing neurons in this region increases plasma glucose and glucagon, lowers insulin levels and stimulates feeding, while inhibition reduces blood glucose, raises insulin levels and suppresses feeding. These results suggest that pancreatic hormones function as an effector mechanism of central nervous system circuits controlling blood glucose and behaviour. The method we employ obviates the need for permanent implants and could potentially be applied to study other neural processes or used to regulate other, even dispersed, cell types.
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stanley
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Kelly
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.
authors.forename: Kaamashri N
authors.initials: KN
authors.lastname: Latcha
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Schmidt
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Nectow
authors.affiliation: Department of Chemical &Biological Engineering, Center for Biotechnology &Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sauer
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Dyke
authors.affiliation: Department of Chemical &Biological Engineering, Center for Biotechnology &Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA.|Howard Hughes Medical Institute, New York, New York 10065, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D005941:Glucokinase / Q000378:metabolism; D006706:Homeostasis; D007003:Hypoglycemia / Q000378:metabolism; D007328:Insulin / Q000097:blood; D019426:Integrases / Q000378:metabolism; D060526:Magnetic Fields; D051379:Mice; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D010187:Pancreatic Hormones / Q000378:metabolism; D011846:Radio Waves; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology* / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010187:Pancreatic Hormones; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D005293:Ferritins; D005934:Glucagon; D005941:Glucokinase; C045073:Cre recombinase; D019426:Integrases