For a long time, sleep research has assumed that the cerebral cortex — the outer layer of the brain responsible for complex functions like thought and memory — plays a passive role during sleep. Instead, it was believed that deeper parts of the brain, known as subcortical regions, control the process of falling asleep. “Usually, sleep is associated with being controlled by subcortical regions,” said Geoffrey Terral, a neuroscientist at the Albert Einstein College of Medicine in New York. While the cortex shows the slow brain waves characteristic of deep sleep, scientists thought these rhythms were triggered by signals from other parts of the brain. A recent study published in the journal Nature challenges this view. Terral and Renata Batista-Brito, who leads the research lab, discovered a specific group of cells in the cortex that can actually initiate sleep. These cells, called Sst-Chodl neurons, make up just about one percent of the cortex’s inhibitory neurons — cells that reduce the activity of other neurons. When these particular cells were activated in mice, the animals fell asleep, suggesting the cortex itself can start the sleep process. The Sst-Chodl neurons are named after two genes that are active in them. While long-range inhibitory neurons marked by these genes have been studied in monkeys, scientists had struggled to manipulate them in the lab. Using just one of these genes to target the cells was not enough, as it also activated a wide range of other neurons. “A single gene is not able to target these cells,” Batista-Brito explained. Inhibitory neurons make up about 20% of all neurons in the cortex, meaning Sst-Chodl cells are extremely rare — roughly one in every thousand neurons. To isolate these specific cells, Batista-Brito’s team developed a method that only labels the cells when both genes are active. This approach took years to refine, as it required extreme precision. “If you're not really specific, the contaminants are going to be much more dominant than the specific cells,” she said. This breakthrough could lead to new insights into how sleep is regulated and may have implications for treating sleep disorders.