The physiology behind feeding behaviors and metabolism of mammals is complicated, and research on these systems is partly hindered by a lack of tools available to examine how specific cell types in the brain can influence metabolic processes. One brain structure involved in this system, the hypothalamus, contains cells that detect blood sugar; however, this structure is located deep within the brain, making it difficult to study. Recent experiments by Stanley et al. (Nature 531, 647–650; 2016) show that, with genetic manipulation, the activity of mouse hypothalamic neurons can be influenced with radio frequency (RF) or magnetic field stimuli from outside of the animals. This novel technique now allows researchers to delineate important relationships between the hypothalamus and metabolic function not possible with previous methods.

Stanley et al. began their experiments by developing a virus which, when injected into mouse hypothalamus, causes glucose-sensing neurons to express membrane channels that are activated by specific RF stimuli (465 kHz). The mice used were a special strain to ensure that the virus only affected glucose-sensing neurons. Thus, unlike some other forms of neural stimulation, only specific types of neurons were manipulated.

After virus injection, RF stimulation was applied and the blood levels of metabolic hormones and enzymes were examined. By varying the strength of stimulation, Stanley et al. successfully changed the amount of plasma insulin, glucagon, glucose, and expression of a liver enzyme involved in metabolism. The researchers then adjusted their technique to allow them to inhibit, or turn down, the activity of these glucose-sensing neurons. In an additional group of mice, RF stimuli now reversed most of the hormone, enzyme, and blood sugar changes they previously observed with stimulation. Thus, the researchers achieved bidirectional control of these glucose-sensing cells. Additionally, the research team used magnetic field stimulation to confirm that their technique could change the firing activity of these neurons, which couldn't be examined using RF stimuli.

Intriguingly, the group also tested the effects of magnetic fields on feeding behavior of virus-injected mice. When exposed to the strong magnetic fields near an MRI scanner, the mice either increased or decreased food intake depending on the type of virus that was expressed in the hypothalamus. This study demonstrates crucial roles of the hypothalamus in metabolism, and also presents a new method of stimulating and inhibiting neurons deep within the brain for bidirectional control of neurons and animal feeding behavior.