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Activation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasively in vivo increases plasma glucose and glucagon, and suppresses plasma insulin; conversely, remote inhibition of glucose-sensing neurons decreased blood glucose and increased plasma insulin. Remote control of animal behaviour This study describes a new technology that allows neurons to be activated or inhibited remotely in freely moving animals using radio waves or magnetic fields. Jeffrey Friedman and colleagues used an iron-binding protein tethered to a heat-sensitive protein to excite or inhibit neurons in the ventromedial hypothalamic nucleus in mice. Activation of glucose-sensing neurons increased plasma glucose and glucagon, suppressed plasma insulin and increased feeding. Inhibition decreased blood glucose, increased plasma insulin and suppressed the response to hypoglycaemia. As well as enabling remote control of cellular activity in basic research, this approach has potential therapeutic implications as a minimally invasive alternative to deep brain stimulation. 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).sup.1. 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.sup.2. 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., Author(s): Sarah A. Stanley [sup.1] , Leah Kelly [sup.1] , Kaamashri N. Latcha [sup.1] , Sarah F. Schmidt [sup.1] , Xiaofei Yu [sup.1] , Alexander R. Nectow [sup.1] , Jeremy [...]

Means for temporally regulating gene expression and cellular activity are invaluable for elucidating underlying physiological processes and would have therapeutic implications. Here we report the development of a genetically encoded system for remote regulation of gene expression by low-frequency radio waves (RFs) or a magnetic field. Iron oxide nanoparticles are synthesized intracellularly as a GFP-tagged ferritin heavy and light chain fusion. The ferritin nanoparticles associate with a camelid anti-GFP-transient receptor potential vanilloid 1 fusion protein, αGFP-TRPV1, and can transduce noninvasive RF or magnetic fields into channel activation, also showing that TRPV1 can transduce a mechanical stimulus. This, in turn, initiates calcium-dependent transgene expression. In mice with stem cell or viral expression of these genetically encoded components, remote stimulation of insulin transgene expression with RF or a magnet lowers blood glucose. This robust, repeatable method for remote regulation in vivo may ultimately have applications in basic science, technology and therapeutics., Studying the actions of specific cells and gene products in vivo is essential for understanding their physiological roles. Cellular activity and/ or gene expression can be regulated by several approaches [...]