Mouse study reveals mechanism driving first night insomnia

You check into a hotel and toss and turn all night, but your sleep improves the following night. Scientists at Nagoya University wanted to understand why this happens. Working with mice, they have identified a group of neurons that become active when an animal enters a new environment. These neurons release a molecule called neurotensin that maintains wakefulness. The effect protects them from potential dangers in unknown surroundings. The study was published in Proceedings of the National Academy of Sciences.

This discovery may explain the "first night effect" seen in humans. On the first night in a new place, the brain remains more vigilant, almost as if acting as a night guard. It keeps one eye open until it confirms the environment is safe. This response evolved to enhance survival. Although this sleep disturbance has been recognized for decades, the brain mechanism behind it had remained unclear. 

"The extended amygdala is a brain region that processes emotions and stress in mammals. Within this region, specific neurons called IPACL CRF neurons produce neurotensin and activate when sensing a new environment," said Daisuke Ono, senior author and lecturer at Nagoya University's Research Institute of Environmental Medicine. "Neurotensin then affects the substantia nigra, a brain area that controls movement and alertness." 

The researchers studied mice in new cages and recorded their brain activity. IPACL CRF neurons became highly active in their new environments. When these neurons were artificially suppressed, the mice fell asleep quickly, even in new environments. When they were activated, the mice stayed awake longer. The team showed that IPACL CRF neurons use neurotensin to communicate with the substantia nigra. 

Because the extended amygdala and substantia nigra exist in all mammals, researchers believe similar circuits likely operate in humans. The findings could lead to new treatments for insomnia and anxiety disorders. Many people with PTSD or chronic stress experience excessive nighttime alertness. Drugs that target this neurotensin pathway could help them sleep.