TThe human brain is a vast network of billions of neurons. By exchanging signals that depress or excite each other, they generate patterns that travel through the brain up to 1,000 times per second. For more than a century, this dizzyingly complex neuronal code has been considered 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 recent 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 inadequate for understanding how the brain works. Experiments in mice, zebrafish and fruit flies reveal that large brain cells called astrocytes serve as supervisors. Once thought of as mere support cells for neurons, astrocytes are now thought to help fine-tune brain circuits, thereby controlling overall brain state or mood—say, our level of alertness, anxiety, or apathy.
Astrocytes, which outnumber neurons in many areas of the brain, have complex and varied shapes and sometimes tendrils that can wrap around hundreds of thousands or millions of synapses, the junctions where neurons exchange molecular signals. This anatomical arrangement perfectly positions astrocytes to influence the flow of information, although whether or how they alter activity at synapses has long been controversial, in part because the mechanisms of potential interactions have not been fully understood. In revealing how astrocytes moderate synaptic conversations, new studies make it impossible to ignore the influence of astrocytes.
“We live in the age of connectomics, where everyone likes to say [that] if you understand the context [between neurons]we can understand how the brain works. That is not true,” he said Marc Freemandirector of the Vollum Institute, an independent neuroscience research center at Oregon Health & Science University, who led one of the new studies. “You can get dramatic changes in neuronal firing patterns with zero changes.” [neuronal] connectivity.”
Astrocytes do not engage in the rapid 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, called neuromodulation, can cause the animal’s brain to switch between dramatically different states, such as gauging when an action is futile and prompting the animal to give up, one of the new papers shows.
Neuromodulation is necessary to keep the level of brain activity within a functional range to prevent it from flattening or bursting into seizures. “No neural circuit would function at all without constant fine-tuning by these things we call neuromodulators.” [the molecules that mediate the adjustments]he said Stephen Smithprofessor emeritus of neuroscience at Stanford University, who conducted pioneering experiments in astrocytic signaling in the late 1980s and early 1990s and was not involved in the new research.
For many years, it was thought that this fine-tuning was done by the neurons themselves. While previous work has implicated astrocytes in some cellular signaling, the latest experiments use “advanced techniques to really pinpoint and satisfy beyond doubt that astrocytes play a key role in neuromodulation in the brain,” he said. Douglas Fieldsa neuroscientist emeritus at the National Institutes of Health who was not involved in the new research.
In this role, astrocytes could be major participants in sleep or psychiatric disorders that broadly disrupt brain states. “We need 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 cobble together the brain and fill the space between neurons like packing peanuts. The Greek word for “glue” and the name “glia” reflect the idea from the mid-18th century that the purpose of the cells was simply to hold the brain together.
By the 1950s, scientists knew that astrocytes could do more than that. In the experiments, cells absorbed excess neurotransmitters, buffered potassium, and secreted substances that neurons need for energy. Like cellular alchemists, astrocytes appeared to monitor and adjust the broth in the brain, maintaining favorable conditions for neurons. But scientists thought of them as relatively passive regulators until the late 1980s, when Smith built a new microscope for his neuroscience lab at Yale University.
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