Some neurons in the basal forebrain produce the chemical acetylcholine. These cells are very active during wakefulness when an animal or human is aroused and attentive. Previous studies have shown that orexin neurons project to these cells, sending positive signals downstream to help keep them active. The new study, however, shows that these acetylcholine-producing neurons, or cholinergic cells, are upstream of the orexin neurons as well ?the two send positive, reinforcing signals back and forth.
"By being active, animals fire up their cholinergic cells, which feed back to orexin neurons positively, and orexin neurons feed back to cholinergic cells," Dr. Yanagisawa said. "This creates a self-reinforcing loop, a positive feedback system that's very important to consolidating wakefulness."
Dr. Yanagisawa said the trigger that causes the sleep "seesaw" to tip from one side to the other and maintain a proper balance between time spent awake and time spent asleep is still a big mystery in brain science. By shedding light on the network of neural connections involved in sleep, he said, his and other studies will help unravel the mechanisms involved in sleep homoeostasis.
In addition to his laboratory at UT Southwestern, Dr. Yanagisawa also directs the ERATO Yanagisawa Orphan Receptor Project in Japan, where these studies were carried out. He and his colleague, Dr. Takeshi Sakurai of the University of Tsukuba, lead author on the study, discovered orexin in 1998 when Dr. Sakurai was a postdoctoral researcher in Dr. Yanagisawa's UT Southwestern lab.