Author: Stanley SA1, Kelly L1, Latcha KN1, Schmidt SF1, Yu X1, Nectow AR1, Sauer J2, Dyke JP3, Dordick JS2, Friedman JM1,4.
1Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA. 2Department of Chemical &Biological Engineering, Center for Biotechnology &Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA. 3Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA. 4Howard Hughes Medical Institute, New York, New York 10065, USA.
Date published: 2016 Mar 23
Other: Special Notes: doi: 10.1038/nature17183. [Epub ahead of print] , Word Count: 212
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.
PMID: 27007848 [PubMed - as supplied by publisher]