Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism.

Publication Type	Academic Article
Authors	Stanley S, Kelly L, Latcha K, Schmidt S, Yu X, Nectow A, Sauer J, Dyke J, Dordick J, Friedman J
Journal	Nature
Volume	531
Issue	7596
Pagination	647-50
Date Published	03/23/2016
ISSN	1476-4687
Keywords	Blood Glucose, Eating, Magnetic Fields, Neurons, Radio Waves, Ventromedial Hypothalamic Nucleus
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.
DOI	10.1038/nature17183
PubMed ID	27007848
PubMed Central ID	PMC4894494