Researchers Discover Rare Cortical Neurons That Can Help Put the Brain to Sleep
Study published in Nature challenges a century-old view of how the brain controls sleep
Cortical long-range inhibitory interneurons help synchronize activity across widely separated cortical regions and promote sleep. Credit: Charlie Padgett
What makes the brain fall asleep? For nearly a century, scientists have looked to structures deep within the brain for the answer. In the traditional view, these regions control when we sleep and wake, while the cerebral cortex—the part of the brain involved in perception, thought, and memory—is largely a passive follower.
A new study led by Renata Batista-Brito, PhD, Associate Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai, and published in Nature, suggests that this picture is incomplete.
The study team discovered an extraordinarily rare population of neurons in the cortex—called Sst-Chodl neurons— that can synchronize activity across large areas of the brain and promote sleep. The findings suggest that the cortex is not simply put to sleep by the rest of the brain; it actively helps put the brain to sleep.
The findings point toward a broader change in how scientists think about sleep. Rather than being controlled only by specialized centers deep within the brain, sleep may emerge from an interaction between those systems and the cortex itself.
“The traditional view of the cortex is as a passive follower during sleep,” said Dr. Batista-Brito, senior author of the paper. “What we found is that the cortex itself contains circuits that can actively drive and synchronize the activity associated with sleep and, when activated, can actually promote sleep.”
The research was conducted while Dr. Batista-Brito and her laboratory were based at Albert Einstein College of Medicine. She recently joined the Icahn School of Medicine, where her laboratory continues to investigate how cortical circuits regulate sleep and behavioral state.
Rare Sst-Chodl Neurons Have Unusual Long-Range Connections
Sst-Chodl neurons are exceptionally rare, making up roughly 0.2% of neurons in the cortex. Unlike most inhibitory neurons, which mainly communicate with nearby cells, these neurons send signals across long distances. This gives the small population the potential to influence activity across large areas of the cortex.
The research team observed that when mice were awake and alert, these neurons were largely quiet. As the animals became drowsy and entered deep non-rapid eye movement (NREM) sleep—the quiet, restful phase of the sleep cycle characterized by slowed breathing, reduced muscle activity, and distinct brain-wave patterns—Sst-Chodl cells became active as the cortex shifted into the slow, synchronized rhythms characteristic of sleep.
But were they simply following the brain into sleep—or helping take it there?
When researchers activated these Sst-Chodl neurons, electrical signals across the neocortex became slower and more synchronized, resembling the cortical activity characteristic of sleep. This manipulation was also sufficient to promote sleep, causing mice to fall asleep more readily and spend more time sleeping.
“These neurons don't simply become active when the animal sleeps,” Dr. Batista-Brito said. “They can actually help drive the transition toward sleep.”
An Evolutionarily Conserved System
Despite being extraordinarily rare, Sst-Chodl neurons have been preserved across hundreds of millions of years of evolution, from amphibians and reptiles to humans.
“Evolution has held onto these cells for an incredibly long time, even though there are very few of them,” Dr. Batista-Brito said. “That suggests they are doing something important. Until now, we knew surprisingly little about what that was.”
The study, conducted in mice, establishes their role in cortical synchronization and sleep. Their extraordinary evolutionary conservation raises the possibility that they perform a similarly fundamental function in other animals, potentially including humans.
Could Sst-Chodl Neurons Help Sense the Brain’s Need for Sleep?
The discovery raised another question: Could Sst-Chodl neurons help translate the brain’s need for sleep into sleep itself?
“As we stay awake, sleep pressure builds until eventually the brain has to sleep,” Dr. Batista-Brito said. “One possibility we are interested in investigating is whether these neurons help sense or enforce that need, pushing the cortex toward sleep when we become too tired. We don't know that yet—but it is an exciting hypothesis we plan to test.”
What Happens When Sleep Goes Wrong? Discovery Opens New Avenues for Studying Sleep Disorders
Sleep is disrupted in many neurological, neurodevelopmental, and psychiatric disorders, including Alzheimer's disease and autism spectrum disorder. Researchers can now ask whether these ancient cortical neurons are altered when normal sleep breaks down.
“Are these neurons functioning normally when sleep becomes disrupted? Could changes in this system contribute to sleep problems in disease?” Dr. Batista-Brito posited. “We don't know yet, but now we have a specific circuit to investigate.”
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. The Graduate School of Biomedical Sciences offers 12 degree-granting programs, conducts innovative basic and translational research, and trains more than 470 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 90th percentile of U.S. private medical schools in Sponsored Programs Direct Expenditures per Principal Investigator, according to the Association of American Medical Colleges. More than 6,900 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.