The human brain is a vast network of billions of neurons. By exchanging signals to depress or excite each other, they generate patterns that ripple across the brain up to 1,000 times per second. For more than a century, that dizzyingly complex neuronal code was thought to be the sole arbiter of perception, thought, emotion, and behavior, as well as related health conditions. If you wanted to understand the brain, you turned to the study of neurons: neuroscience.
But a recent body of work from several labs, published as a trio of papers in Science in 2025, provides the strongest evidence yet that a narrow focus on neurons is woefully insufficient for understanding how the brain works. The experiments, in mice, zebra fish, and fruit flies, reveal that the large brain cells called astrocytes serve as supervisors. Once viewed as mere support cells for neurons, astrocytes are now thought to help tune brain circuits and thereby control overall brain state or mood — say, our level of alertness, anxiousness, or apathy.
Astrocytes, which outnumber neurons in many brain regions, have complex and varied shapes, and sometimes tendrils, that can envelop hundreds of thousands or millions of synapses, the junctions where neurons exchange molecular signals. This anatomical arrangement perfectly positions astrocytes to affect information flow, though whether or how they alter activity at synapses has long been controversial, in part because the mechanisms of potential interactions weren’t fully understood. In revealing how astrocytes temper synaptic conversations, the new studies make astrocytes’ influence impossible to ignore.
“We live in the age of connectomics, where everyone loves to say [that] if you understand the connections [between neurons], we can understand how the brain works. That’s not true,” said Marc Freeman, the director of the Vollum Institute, an independent neuroscience research center at Oregon Health and Science University, who led one of the new studies. “You can get dramatic changes in firing patterns of neurons with zero changes in [neuronal] connectivity.”
Astrocytes do not engage in the rapid-fire signaling typical of neurons at synapses. Instead, they monitor and tune higher-level network activity, dialing it up or down to maintain or switch the brain’s overall state. This function, termed neuromodulation, may cause an animal’s brain to switch between dramatically different states, such as by gauging when an action is futile and prompting the animal to give up, one of the new papers shows.
Neuromodulation is necessary for keeping the brain’s activity level in a functional range, preventing it from either flatlining or erupting in seizures. “No neural circuit would work at all without continual fine-tuning by these things we call neuromodulators, [the molecules that mediate the adjustments],” said Stephen Smith, an emeritus professor of neuroscience at Stanford University who conducted pioneering experiments in astrocyte signaling in the late 1980s and early 1990s and was not involved in the new research.
For many years, that fine-tuning was thought to be conducted by neurons themselves. While previous work has implicated astrocytes in some cellular signaling, the latest experiments use “advanced techniques to really pinpoint and satisfy beyond a doubt that astrocytes are having a key role in neuromodulation in the brain,” said Douglas Fields, an emeritus neuroscientist at the National Institutes of Health who was not involved in the new research.
In that role, astrocytes could be major participants in sleep or psychiatric disorders that broadly disrupt the state of the brain. “We have to think about what this means for neuropsychiatric disease,” Freeman said.
A Star Is Born
Astrocytes are a type of glial cell, a class of non-neuronal nervous system cells that tile the brain, filling the space between neurons like packing peanuts. Greek for “glue,” the name “glia” reflects the mid-18th-century idea that the cells’ purpose was simply to hold the brain together.
By the 1950s, researchers knew that astrocytes did more than that. In experiments, the cells sucked up excess neurotransmitters, buffered potassium, and secreted substances that neurons require for energy. Like cellular alchemists, astrocytes seemed to be monitoring and adjusting the broth of the brain, keeping conditions favorable for neurons. But scientists considered them relatively passive regulators until the late 1980s, when Smith built a new microscope for his neuroscience lab at Yale University.
