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$1.5 Million Grant to Yale for Narcolepsy-Neurotransmitter Study

Yale School of Medicine researchers have received a $1.5 million grant from the National Institutes of Health (NIH) to study neurons// that play a major role in narcolepsy.

Narcolepsy is a neurodegenerative disease characterized by daytime sleepiness. The NIH grant will further Yale research into narcolepsy and other disorders linked to neurons that produce the peptide hypocretin.

“The activity of these hypocretin cells is important for enhancing cognitive arousal and resisting sleep, and they may also play a role in anxiety and body weight regulation,” said the principal investigator, Anthony van den Pol, neurosurgery professor.

He said neurons send out long fibers, or axons, to other nerve cells and release either an inhibitor or excitatory neurotransmitter onto their target cells. A small number of these neurons make and secrete the transmitter hypocretin.

Hypocretin neurons actually make two neurotransmitters, hypocretin and dynorphin. The results of Van den Pol’s recent work, published in the Journal of Neuroscience, shows that these two transmitters, or peptides, have actions that oppose each other. Hypocretin increases the excitability of other nerve cells, whereas dynorphin inhibits the activity.

Van den Pol and first author, Ying Li, an associate research scientist, wondered what cellular value opposing neurotransmitters might have. They found that different target neurons in the brain show different responses to co-stimulation by the two peptides.

They came to this finding by using whole cell patch clamp recording, in which an ultra-thin glass pipette, like a very small straw, is used to record the electrical activity caused by movement of ions through channels in single nerve cells.

Van den Pol said that these neurotransmitters had different effects on different cell types. One target, MCH neurons, were excited by hypocretin but inhibited by dynorphin.

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