Flipping a Switch Inside the Head

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With new technology, scientists are able to exert wireless control over brain cells of mice with just the push of a button. The first thing they did was make the mice hungry.

READY YOUR TINFOIL HATS—mind control is not as far-fetched an idea as it may seem. In Jeffrey M. Friedman’s laboratory, it happens all the time, though the subjects are mice, not people.

Friedman and his colleagues have demonstrated a radio-operated remote control for the appetite and glucose metabolism of mice—a sophisticated technique to wirelessly alter neurons in the animals’ brains. At the flick of a switch, they are able to make mice hungry—or suppress their appetite—while the mice go about their lives normally. It’s a tool they are using to unravel the neurological basis of eating, and it is likely to have applications for studies of other hard-wired behaviors.

Friedman, Marilyn M. Simpson Professor, has been working on the technique for several years with Sarah Stanley, a former postdoc in his lab who now is assistant professor at the Icahn School of Medicine at Mount Sinai, and collaborators at Rensselaer Polytechnic Institute. Aware of the limitations of existing methods for triggering brain cells in living animals, the group set out to invent a new way. An ideal approach, they reasoned, would be as noninvasive and non-damaging as possible. And it should work quickly and repeatedly.

Although there are other ways to deliver signals to neurons, each has its limitations. In deep-brain stimulation, for example, scientists thread a wire through the brain to place an electrode next to the target cells. But the implant can damage nearby cells and tissues in ways that interfere with normal behavior. Optogenetics, which works similarly but uses fiber optics and a pulse of light rather than electricity, has the same issue. A third strategy—using drugs to activate genetically modified cells bred into mice—is less invasive, but drugs are slow to take effect and wear off.

The solution that Friedman’s group hit upon, referred to as radiogenetics or magnetogenetics, avoids these problems. With their method, published last year in Nature, biologists can turn neurons on or off in a live animal at will—quickly, repeatedly, and without implants—by engineering the cells to make them receptive to radio waves or a magnetic field.

By W. Wayt Gibbs

Read Full Article on Rockefeller.edu

Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism


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)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 neurons2. 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. (See Original Article)

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