Appetite and other deep-seated desires could be modified by altering brain ion channels, according to research at Janelia Farm.

Scott Sternson has always wondered what drives behavior, especially those fundamental motivations required for survival. Hunger, for example, is so crucial that it must be evolutionarily “hard-wired” deep within the brain. After all, as Sternson observes, “if the animal doesn’t eat, it dies.”

Melding the diverse disciplines of synthetic chemistry, structural biology, and computational modeling, Sternson and Loren Looger, both group leaders at HHMI’s Janelia Farm Research Campus, have uncovered clues about the brain circuitry that controls deep-seated behaviors, like that irresistible urge to visit the dessert table.

The pair devised a noninvasive method to stimulate individual brain neurons or clusters of neurons in live, conscious animals—a remote control for the brain, of sorts. They demonstrated the technique by converting gluttonous mice into champion dieters. The researchers published their findings September 2, 2011, in Science.

You can blame those dessert cravings in part on ion channels, explains Sternson. Ion channels are molecular pores, donut-shaped proteins embedded in the surface of neurons that allow charged particles to enter and exit the cells. Like a subway system’s turnstiles, ion channels have moving parts, opening and closing to ensure passage of only the proper type of ion, single file, by the millions every second. Like their mass transit counterparts, some ion channels, called ligand-gated ion channels, won’t budge until presented with a ticket—in this case, a chemical neurotransmitter. The ensuing electrochemical impulses that race through neurons create thoughts, emotions, and, ultimately, behavior.

Sternson’s scientific interest in hunger began when he was a postdoc in the laboratory of HHMI investigator Jeffrey Friedman at the Rockefeller University. In the mid-1990s, Friedman identified a hormone called leptin that exerts powerful control on appetite by acting on a region of the brain called the hypothalamus. Sternson’s goal was to understand the neuronal wiring in the hypothalamus that controls appetite. He wanted to identify the different neurons and deduce the contribution of each toward evoking hunger. The problem was that no tools were available to systematically probe brain wiring with the precision he needed.

Illustration: Jing Wei

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