Study Pinpoints Brain Activity Related to Reducing Drowsiness

A small set of neurons responsible for keeping people alert have the ability to arouse each other, a finding that could have implications for those who work long or odd hours and have difficulty staying awake, a Yale researcher has found.

Anthony van den Pol, professor of neurosurgery at the Yale School of Medicine and senior author of the study published this month in the journal, Neuron, used transgenic mice in which the hypocretin neurons were green, and then monitored the cellular activity of the green cells. These neurons are located in the hypothalamus, a part of the brain that regulates food intake, the hormone system, and biological rhythms.

Van den Pol said the goal of the study was to map the physiological characteristics of the hypocretin neurons and the feedback effects of hypocretin and other neurotransmitters on hypocretin neurons. One problem in doing this in the past was that it was difficult to locate these neurons in the brain slices as they constitute only a small percentage, about 10 percent, of cells in the lateral hypothalamic area. However, by looking for green nerve cells, the scientists could focus on the hypocretin neurons.

“We found they have an ability to excite each other at the cellular level,” said van den Pol. “It’s like turning on the ignition in a car, that in turn activates a number of different automobile circuits, getting the car ready to drive away.” In contrast, another neurotransmitter, norepinephrine, inhibits the hypocretin cells, acting as the brakes for the hypocretin system.

Although the brain has many hundreds of millions of cells, van den Pol said there are only a few thousand of these particular neurons in the brain, and they are spread over a wide area. He and his colleagues were interested in finding out what turns the system on and what turns it off. It was van den Pol’s laboratory that first reported that hypocretin was a new excitatory neurotransmitter. The absence of hypcretin causes narcolepsy, a condition characterized by an uncontrollable desire to sleep.

“If the neural arousal system is overly excited, a person might become manic,” he said. “If under aroused, a person might have become excessively sleepy. These studies may point us in a direction to help people who have to work long hours or at unusual times of the night. Maybe there is a way to facilitate their performance and cognitive state using the hypocretin system.”

Other scientists on the study were first author Ying Li and co-authors Xiao-Bing Gao and Takeshi Sakurai.

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