‘Satiety Center’ Of The Mouse Brain
By pitting two forces — hunger and circadian rhythms — against each other, researchers at Rockefeller University have identified the region of the mouse brain that first registers changes in food availability. The research, as aforesaid in mice, suggests that shifting the timing of a meal increases mental alertness even during times when they are usually at rest, findings that, perhaps, may have implications for targeting health concerns such as obesity and diabetes as well as optimizing performance on tasks that require sustained vigilance in humans.
To pit the need for food against the need for sleep, scientists led by Donald Pfaff, head of the Laboratory of Neurobiology and Behavior, gradually shifted the mice’s mealtime during the night, when mice are most active, to a four-hour window during the day, when they are usually at rest. Three days after the mealtime shift, the mice began to show classic signs of anticipatory behavior: wheel-running an hour or two before the timed meal. Compared to control animals, the shifted mice ran three times the distance on the wheel — increased activity signaling a heightened sense of alertness. This behavior also suggests that the light-dark cycle no longer regulated the mice’s behavioral arousal; food did.
The researchers used immunocytochemistry to test where in the brain these two arousal pathways converge. Out of the 16 brain regions tested, only one had become activated: the ventromedial hypothalamus, a group of neurons known as the satiety center of the brain. Animals, including humans, tend to stop eating when this region is activated, and damage to this group of neurons leads to obesity. The activity of the paraventricular nucleus, a region that produces many hormones, was decreased.
“Since we examined the brain as close as possible to the development of this anticipatory behavior,” says postdoc Ana Ribeiro, “the neuronal changes we observed are the ones most likely causing the changes in behavioral arousal. These regions are thus the best targets for modulating arousal.”
As about implications for humans, first author Ribeiro daringly claims that to optimize performance on tasks that require sustained vigilance, ones performed by air-traffic controllers, physicians, the military and others, understanding the neural mechanisms and molecules involved in mediating arousal becomes important. “This research,” she says, “gives us a big clue as to what these mechanisms may be.”
PNAS | December 11, 2007 | vol. 104 | no. 50 | 20078-20083
Two forces for arousal: Pitting hunger versus circadian influences and identifying neurons responsible for changes in behavioral arousal
Ana C. Ribeiro*,, Evelyn Sawa*, Isabelle Carren-LeSauter*, Joseph LeSauter, Rae Silver,,¶, and Donald W. Pfaff*,
*Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021; Department of Psychology, Barnard College, New York, NY 10027; Department of Psychology, Columbia University, New York, NY 10027; and ¶Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
Contributed by Donald W. Pfaff, October 24, 2007 (received for review July 6, 2007)
The mechanisms underlying CNS arousal in response to homeostatic pressures are not known. In this study, we pitted two forces for CNS arousal against each other (circadian influences vs. restricted food availability) and measured the neuronal activation that occurs in a behaviorally defined group of animals that exhibited increased arousal in anticipation of feeding restricted to their normal sleeping time. The number of c-FOS+ neurons was significantly increased only in the ventromedial nucleus of the hypothalamus (VMH) in these mice, compared with control animals whose feeding was restricted to their normal active and feeding time (P < 0.01). Because the activation of VMH neurons coincides with the earliest signs of behavioral arousal preceding a change in meal time, we infer that VMH activation is involved in the increased arousal in anticipation of food.
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