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Researchers at the University of Basel published a study in Nature on August 19, 2026, identifying specific nerve cell populations in the mouse brain that activate during prolonged wakefulness and actively drive the physiological need for sleep. Led by Prof. Dr. Alex Schier at the Biozentrum of the University of Basel, alongside collaborators from Beth Israel Deaconess Medical Center and Auburn University, the team mapped the neural circuits responsible for regulating sleep pressure after long periods of wakefulness.
Mapping the Neural Circuit of Sleep Pressure
To pinpoint which brain regions control sleep demand, the research team compared brain activity across normal sleep-wake cycles, periods of sleep deprivation, and subsequent recovery sleep. Computer-aided analysis of whole-brain data was managed by a team led by Prof. Dr. Ivan Dokmanić at the Center for Data Analytics at the University of Basel. Within a key brainstem region, scientists found that two distinct neuronal populations—GABAergic and serotonergic neurons—increased their activity steadily as wakefulness lengthened, and their activity dropped sharply once sleep commenced.
“We have identified neuronal populations that register longer wake phases and actively promote sleep,” Prof. Dr. Alex Schier said. “This is an important puzzle piece to understand why we get tired.”
Testing the Function of GABAergic and Serotonergic Neurons
To determine whether these two nerve cell types merely mirrored sleep need or actively created it, the investigators manipulated their activity in laboratory mice. When researchers simultaneously activated the GABAergic and serotonergic neurons in the brainstem, the animals fell into a deeper and longer recovery sleep resembling the natural aftermath of extended wakefulness. Conversely, inhibiting these specific cells caused the mice to sleep significantly less, allowing them to remain awake and alert for much longer periods.
“These neurons therefore not only signal that an animal has been awake for a long time,” Prof. Dr. Alex Schier explained. “Our experiments show that they play a decisive role in promoting sleep and that they are potentially central components of the neural network that generates sleep pressure.”
Behavioral Impacts of Long-Term Neuronal Inhibition
Further experiments involving the long-term suppression of these GABAergic and serotonergic populations revealed a dramatic drop in total sleep demand. The test mice slept roughly 70 percent less than normal. Surprisingly, despite the severe reduction in rest, most of the subjects did not display the heavy behavioral impairments typically tied to acute sleep deprivation.
According to Dr. William Joo, the study’s first author, this discovery opens up entirely new avenues for sleep research. “Since we can target and alter sleep behavior, we can now investigate how organisms adapt to long-term sleep deprivation,” Dr. Joo stated. “That could point to new ways to improve resilience against sleep deprivation and other physiological stresses.”