A research team in Japan led by Nagoya University has found a new neural pathway that connects the circadian clock, stress and vigilance in mammals. The team identified a neuron called a corticotropin releasing factor (CRF) neuron that becomes overly active when the mammal is under stress, which could trigger insomnia and other sleep disorders. Their results were recently published in the journal Science Advances.
Living organisms have a 24-hour cycle called the circadian rhythm. In mammals, the central circadian clock, located in the neurons of the suprachiasmatic nucleus (SCN) of the brain, regulates the sleep-wake rhythm. In life-threatening situations, however, the circadian rhythm signal is turned off to keep the animal awake so that even when it is normally time to sleep, it can escape the danger. Although temporarily turning off the sleep-wake cycle is essential for survival, excessive or prolonged stress from such dangers can trigger insomnia and other sleep disorders.
“It is known that the circadian clock and stress have an impact on sleep, but it was unclear which nerve pathway is decisive for the circadian regulation of sleep and wakefulness,” says Dr. Daisuke Ono of the Environmental Medicine Research Institute at Nagoya University. To determine the path, a research team from Nagoya University led by Prof. Akihiro Yamanaka and Dr. Ono carried out a study with mice in collaboration with Takashi Sugiyama of Olympus Corporation in Japan.
Researchers focused on CRF neurons – known to play a role in the stress response – located in the paraventricular core of the hypothalamus. They investigated how sleep and wakefulness would affect mice if the CRF neurons were activated. The results showed that the activated CRF neurons kept the animals awake and made them move vigorously, suggesting that their wakefulness was promoted. The researchers also observed that CRF neurons remained active when the mice were awake and that when the activity of the neurons was suppressed, the animals’ wakefulness and locomotor activity were reduced.
Further research also showed that inhibitory neurons in the SCN called GABAergic neurons play a significant role in regulating the activity of CRF neurons and that activation of CRF neurons stimulates orexin neurons in the lateral hypothalamus, which leads to the promotion of wakefulness .
The team therefore concluded that GABAergic neurons in the SCN control the activity of CRF neurons, which ultimately regulate the sleep-wake cycle. “We identified this nerve path in mice, which are nocturnal animals. Further studies are needed to elucidate how the nocturnal and diurnal differences are regulated in the brain, ”says Dr. Ono.
“Sleep disorders are a serious problem in today’s society. We hope that our results will help develop new therapies for insomnia and other sleep disorders caused by stress or a disturbed circadian rhythm.”
Materials provided by Nagoya University. Note: The content can be edited for style and length.