Research shows how stress activates neurons that disrupt sleep

New research reveals that neurons in the preoptic hypothalamus, the region of the brain that regulates sleep and body temperature, are rhythmically activated during non-rapid eye movement (NREM) sleep. Stress activates these brain cells in turn, causing “microarousals” that interrupt sleep cycles and decrease the length of sleep episodes, according to a study from the Perelman School of Medicine at the University of Pennsylvania, published in Current biology.

While our body is at rest when we sleep, our brain is still very active during four different stages of sleep. In each 90-minute sleep cycle, there are three stages of NREM sleep and one stage of rapid eye movement (REM) sleep.

During the first two stages of NREM sleep, brain waves, heart rate and breathing slow and body temperature decreases. The second stage also includes unique brain activity, called spindles and K complexes, which are short bursts of activity responsible for processing external stimuli, as well as memory consolidation.

The third stage of the NREM sleep cycle is where the body releases growth hormone, which is important for repairing the body, keeping the immune system healthy, and further improving memory.

During the third phase, brain waves are larger, called delta waves. REM sleep, which occurs in that phase where dreaming normally occurs, is also essential for memory formation, emotion processing, and brain development.

“When you have a bad night’s sleep, you notice that your memory is not as good as it normally is or that your emotions are all over the place, but a bad night’s sleep interrupts many other processes throughout your body . is even more pronounced in people with stress-related sleep disorders,” said lead author Shinjae Chung, Ph.D., assistant professor of neuroscience.

“It is crucial to understand the biology that determines brain activity during these crucial stages of sleep, and how stimuli like stress can disrupt it, so that we can one day develop therapies to help individuals have a better more restorative sleep that allows their brains to complete these important processes.”.

Researchers monitored activity in the preoptic area (POA) of the hypothalamus of mice during natural sleep and found that glutamatergic neurons (VGLUT2) are rhythmically activated during NREM sleep. They also found that VGLUT2 neurons were more active during wakefulness and less active during NREM and REM sleep.

During microarousals from NREM sleep, VGLUT2 neurons were the only active neurons within the POA, and their signals began to increase before a microarousal.

To confirm that active VGLUT2 neurons were indeed the cause of the microarousals, the researchers stimulated VGLUT2 neurons in sleeping subjects, which immediately increased the number of microarousals and wakefulness.

Next, to illustrate the link between stress and increased activation of VGLUT2 neurons, the researchers exposed subjects to a stressor, which increased wake time and microarousals, and decreased overall time spent in paradoxical and NREM sleep.

The researchers also noted increased activity of VGLUT2 neurons during NREM sleep in stressed subjects. Additionally, when researchers inhibited VGLUT2 neurons, microarousals during NREM sleep decreased and NREM sleep episodes were longer.

“Glutamatergic neurons in the hypothalamus give us a promising target for developing treatments for stress-related sleep disorders,” said first author Jennifer Smith, a graduate researcher in Chung’s lab.

“Being able to reduce interruptions during important stages of non-REM sleep by suppressing VGLUT2 activity would be revolutionary for people struggling with sleep disturbances due to disorders like insomnia or PTSD.”