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

The findings are published in Current Biology in an article titled, “Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons.”

“When you have a bad night of sleep, you notice that your memory isn’t as good as it normally is, or your emotions are all over the place—but a bad night of sleep interrupts so many other processes throughout your body. This is even more heightened in individuals with stress-related sleep disorders,” said senior author, Shinjae Chung, PhD, an assistant professor of neuroscience. “It’s crucial to understand the biology driving the brain activity in these crucial stages of sleep, and how stimuli like stress can disrupt it, so that we might someday develop therapies to help individuals have more restful sleep that allows their brain to complete these important processes.”

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

During microarousals in NREM sleep, VGLUT2 neurons were the only active neurons within the POA, and their signals started to increase in the time before a microarousal. To confirm that active VGLUT2 neurons were indeed the cause of microarousal, the researchers stimulated the VGLUT2 neurons in sleeping subjects, which immediately increased the amount of microarousals and wakefulness.

To illustrate the connection between stress and increased VGLUT2 neuron activation, researchers exposed subjects to a stressor, which increased awake time and microarousals, and decreased overall time spent in REM and NREM sleep. Researchers also noted increased VGLUT2 neuron activity during NREM sleep in the stressed subjects. What’s more, when researchers inhibited VGLUT 2 neurons, microarousals during NREM sleep decreased, and NREM sleep episodes were longer.

“The 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 the important stages of non-REM sleep by suppressing VGLUT2 activity would be groundbreaking for individuals struggling with disrupted sleep from disorders like insomnia or PTSD.”