Optogenetic tools allow researchers to activate or inhibit neurons that express genetically encoded, light-sensitive ion channels by shining light onto the target cells. When applied to the mammalian brain, these techniques require the implantation of either a light-penetrable window in the skull or optical fibers to deliver light to the target neurons. Stanley et al. have developed a noninvasive method for controlling the activity of neurons in the mouse brain. In cells expressing the iron-binding protein ferritin tethered to the cation channel transient receptor potential vanilloid 1 (TRPV1), exposure to radio waves or magnetic fields activates TRPV1, thus allowing calcium (Ca2+) to flow into the cells. The authors expressed two fusion proteins in a hypothalamic neuronal cell line: green fluorescent protein fused to ferritin (GFP-ferritin) and a GFP-binding protein fused to TRPV1 (anti-GFP–TRPV1). Exposure of these cells to 465 KHz radio waves increased intracellular Ca2+ and the expression of Ca2+-responsive genes in a manner that depended on the strength of the field, effects that were abolished with a pharmacological inhibitor of TRPV1. When mice expressing GFP-ferritin and anti-GFP–TRPV1 specifically in glucose-sensitive neurons of the ventromedial hypothalamus were exposed to radio waves or placed near an electromagnet, their blood glucose and food intake increased and circulating insulin decreased as compared with controls. These results were similar to those obtained by activating the same neurons optogenetically. To generate mice in which the same population of neurons could be inhibited, the authors expressed in these neurons GFP-ferritin and a form of anti-GFP–TRPV1 in which TRPV1 was mutated to render it permeable to chloride (anti-GFP–TRPV1mutant). Exposing these mice to radio waves or a magnetic field reduced blood glucose, increased circulating insulin, and inhibited feeding. In addition to illustrating that this population of glucose-sensitive neurons can control organismal metabolism, these results demonstrate the utility of a noninvasive method for controlling neuronal activity. This or a similar system could enable the simultaneous control of neuronal activity across large populations of neurons or in separate populations of neurons without the need for multiple light-delivering implants.
S. A. Stanley, L. Kelly, K. N. Latcha, S. F. Schmidt, X. Yu, A. R. Nectow, J. Sauer, J. P. Dyke, J. S. Dordick, J. M. Friedman, Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature 531, 647–650 (2016). [PubMed]