The Silent Star-Shaped Cells of the Brain Steal the Limelight

How underappreciated astrocytes (the brain’s “silent” glial cells) are working to sculpt neural circuits and behavior

Astrocytes – the long-underestimated star-shaped brain cells – are at last in the spotlight. The glial cells, whose delicate tendrils envelop neurons, constitute about 20–35% of all brain cells. For decades, neuroscientists thought astrocytes simply swept up the detritus and gave neurons a snack. Unlike neurons, astrocytes don’t generate obvious electrical signals, so they were christened “silent”. But new and thrilling research indicates these cells actually eavesdrop on brain chemicals and actively modulate neuronal activity. In short, astrocytes are far from silent.

These findings derive from three separate studies (in fruit flies, zebrafish, and mice) in Science on May 15, 2025. Collectively, they indicate that astrocytes serve as gatekeepers and mediators of brain signaling. When a neuromodulator (a chemical signal that alters brain state, such as dopamine or norepinephrine) surges into the brain, astrocytes can turn on, perceive the message, and then transmit or modulate that message to neurons. In experiments, the activation of these “silent” switches in astrocytes changed animal behavior – from a fruit fly’s reflex to a zebrafish larva’s choice to swim no more.

These results upend 80 years of dogma. As a researcher was quoted, “Textbooks tell us that neuromodulators such as norepinephrine tune neurons directly – in fact, textbooks tell us that everything in the brain is about neurons.” But “it seems that much brain wiring and activity is probably orchestrated by astrocytes, on slower timescales.” This reorientation of thought may reveal new avenues for the treatment of mood and attention disorders, and may even reveal how current drugs (such as antidepressants) work.

What Are Astrocytes – and Why Were They “Silent”?

Astrocytes are a class of glial cells (from Greek glia, or “glue”) named for their star appearance. Their spindly, long arms stretch out to thousands of neurons, enveloping synapses (the points of contact between neurons). Astrocytes were traditionally thought of as the brain’s helpers:

• Cleaning crew and gatekeepers: They sweep away excess neurotransmitters and cellular debris from the space between neurons and assist in the construction of the blood–brain barrier that prevents toxins from entering.
• Nutrient suppliers: They store and distribute glucose and other nutrients to neurons.
• Architects: They direct developing neurons as they make new connections during brain development.

One account points out that for many years, astrocytes were merely “helpers, providing grunt work in the brain.” Even neuroscientists’ focus was neuron-focused: by studying only the electrical firing of neurons, researchers presumed astrocytes were largely passive “wallflowers.” In the words of cell biologist Cagla Eroglu: “They were thought to be silent. That silence might have tricked scientists into thinking astrocytes weren’t significant in transmitting signals.”

So why “silent”?

Unlike neurons, astrocytes don’t fire with sharp voltage spikes. Instead, they talk to other cells using waves of calcium inside the cell or by secreting chemicals. Because they didn’t have clear-cut electrical pulses, initial experiments just wrote them off as not making any contribution. But new technology reveals that astrocytes do react actively to brain chemistry, just weren’t “visible” in past EEG-type recordings. Indeed, each square millimeter of brain tissue is touched by at least one astrocyte. With each of those astrocytes in contact with tens of thousands of synapses, the cells are perfectly placed to feel and mold neural networks.

Figure: Astrocytes (glial cells) with a starburst appearance and extended processes once appeared to be quiet support cells. New findings indicate that these cells (seen here in conjunction with neurons) actively hear chemical signals and regulate neural circuits.

Astrocytes Speak: Recent Findings Across Species

Recent experiments in flies, fish, and mice have uncovered a shared thread: astrocytes do more than provide support to neurons – they actively regulate brain signals. More precisely, researchers discovered that astrocytes can serve as gatekeepers for neuromodulators (brain chemicals determining overall alertness or mood). Simply put, an astrocyte may “sleep” until a specific chemical (such as a threat signal) wakes it up, and the astrocyte then relays that signal to neurons. The trio of Science reports demonstrated that in animals, astrocytes can turn on and off their sensitivities to neurotransmitters, ultimately influencing behavior.

Major findings from the new research are:

• In fruit flies, Astrocytes within the spinal cord-like nerve cord react to the insect neuromodulator tyramine. This message activates astrocytes so they’ll hear other brain chemicals (such as dopamine). When there’s no tyramine, the astrocytes “won’t listen” to dopamine. In one test, scientists discovered that priming astrocytes to be dopaminergic-sensitive caused larvae to roll back over onto their backs more quickly, and blocking dopaminergic sensing by astrocytes slowed them down. Essentially, tyramine served as a “wake-up” signal. Marc Freeman, co-senior author on the fly study, referred to this as “stunning”: “That an arousal cue could turn an astrocyte from not responding to all those big neurotransmitters to suddenly hearing everything … boggles the mind.”
• In zebrafish, Scientists trying to understand how young zebrafish choose to “give up” on an impossible swimming task discovered that astrocytes in the hindbrain of the fish are key to turning off the response. When a fish is caught and continues to swim harder (a reflex of survival), increased concentrations of the arousal chemical norepinephrine cause astrocytes to release ATP into the intercellular space. Enzymes rapidly convert that ATP into adenosine, a confirmed brain relaxation signal. The adenosine binds to neuron receptors, and the fish will give up swimming (as if it is saying “enough” to the hopeless struggle). Stopping the astrocyte-stimulated pathway (for instance, by preventing adenosine from functioning) made the fish continue to try instead of stopping. Briefly, when neurons pass the “stop” message along to astrocytes, the astrocytes’ biochemical sequence of ATP→adenosine is the thing that ceases activity.
• In mice, Washington University researchers found that the mammalian counterpart of this system is also astrocyte-reliant. Norepinephrine (NE) – a stress-and-attention-associated neurotransmitter – typically diminishes synaptic strength between neurons in instances where animals attend or are frightened. The new research demonstrated that astrocytes are necessary for NE to do so. Mice with astrocytic NE receptors missing (or whose astrocytes were knocked down) experienced no NE-induced synaptic alteration. On the other hand, although neurons themselves could not perceive NE, norepinephrine reconfigured the circuit through the astrocytes anyway. The scientists determined that NE prompted astrocytic increases in calcium and release of ATP, which once more converted to adenosine and reduced synaptic activity by acting on neuronal adenosine receptors. As the abstract to the paper stated, this would suggest a new model: astrocytes are “the circuit effector through which norepinephrine produces network and behavioral adaptations.”

Together, the research creates a profile of astrocytes as adaptive middlemen of brain signaling. “It’s not that neurons don’t perceive [the chemical signals],” remarks Eroglu; instead, “the brain isn’t wired that way. It’s wired in a manner where there is an astrocyte go-between.” That is to say, neuromodulators will typically pass through an astrocyte intermediary before acting to drive neural circuits.

How Astrocytes Change Behavior and Brain Circuits

These findings have interesting functional implications. In fly experiments, changes in astrocyte sensitivity affected a larva’s reflex: a test known as the “righting response,” in which a larva turns itself over after it has toppled. Flies whose astrocytes were set to respond to dopamine righted themselves more quickly, indicating that astrocytes facilitated the nervous system’s response to the environment more rapidly. In zebrafish, disabling the astrocyte pathway caused them to swim indefinitely in hopeless situations, while activating it caused them to quit earlier – a matter of life and death in the wild. And in mice, the astrocyte-regulated norepinephrine pathway effectively rewires neural connections during states of enhanced attention or stress.

Astrocytes, therefore, may control anything from a mere reflex to intricate brain state transitions. Brain cells are no longer solitary: the network of astrocytes threads through and governs clusters of several neurons simultaneously. As one scientist explained it, an individual astrocyte “has 100,000 synapses that can transmit signals to other cells. This system enables them to decide which neurons to pay attention to… It puts meaning into the chaos of activity in the brain from moment to moment.”

In real-life terms, consider astrocytes to be switches or strippers in the brain’s messaging. They can “turn on and off different knobs,” according to coauthor Kevin Guttenplan, with measurable impacts on neural circuits and behavior. To illustrate, by flipping the astrocyte response, the system can give priority to certain signals (such as threat messages) while disregarding others – a sort of internal attention switch. As Freeman’s lab explains, if a tiger is coming after you, the brain must eliminate everything else and concentrate on getting away. Astrocytes deliver that cutoff: they assist the brain in paying attention to important messages by selectively passing on only those neurotransmitters essential to the situation.

Step-by-Step: Astrocyte Signaling in Zebrafish

To show this astrocyte function, look at the zebrafish “giving up” study. The scientists dissected the process:

• Futility detected: If a larva swims in vain, its neurons release norepinephrine (NE) as a stress/arousal signal.
• Astrocyte activation: NE activates receptors on neighboring astrocytes, triggering an intracellular increase in calcium.
• ATP release: Activated astrocytes then release ATP into the extracellular space.
• Conversion to adenosine: Extracellular enzymes quickly convert that ATP to adenosine.
• Neuronal inhibition: The adenosine acts on A1 receptors on neurons, which inhibits neural firing. This retards the fish’s thrashing and causes it to desist.

This cascade – NE to astrocyte to adenosine to neuron – renders the choice to “give up” not merely a neural message but a neuron–astrocyte–neuron feedback loop. Inhibition of any astrocyte step (e.g., the calcium increase or the adenosine receptor) interferes with the behavior.

A New Perspective in Mice: Redrawing the Textbooks

In slices of mouse brains, Papouin and coworkers demonstrated that NE added to the slices reduces synaptic strength as predicted, but only if astrocytes are present. If the NE receptors on astrocytes were genetically knocked out, the synapses no longer reacted to NE at all. Papouin highlights the way this turns the conventional account on its head: rather than NE directly acting on neurons, the “second chemical” from astrocytes (ATP/adenosine) carries the load. Even if neurons themselves were not able to detect NE, it might be able to alter connectivity through astrocytes. As Papouin explains, “It seems that a lot of brain wiring and activity is probably orchestrated by astrocytes, on slower timescales.” This discovery rewrites the way we comprehend attention and learning: to rewire the brain in alertness, we require the astrocyte middleman.

Interestingly, in each instance, the output molecule tends to be ATP/adenosine, a major metabolic molecule transformed into a messenger. NE or tyramine in flies and mice activates astrocytes to release ATP, which gets converted to adenosine to regulate synapses. This proposes an evolutionarily conserved cascade: a neuromodulator activates astrocytes, and the astrocytes release a purinergic (ATP/adenosine) signal onto neurons. It’s more of a relay race: neurotransmitter to astrocyte to neuron.

Why This Matters: New Possibilities for Research and Medicine

These findings have significant consequences. In the first place, they call for a more nuanced image of brain operation. Rather than looking at the brain as a clean network of neurons bridged by synapses, we now perceive an additional level of control. “You need the astrocyte intermediary,” says Eroglu. Practically speaking, that means many of the effects we thought were solely neuronal can include astrocytes. For instance, ubiquitous drugs that act on neurotransmitters, such as antidepressant SSRIs (selective serotonin reuptake inhibitors), may also be acting on astrocytes. Astrocytes have many of the same receptors, so SSRIs would have an indirect impact on them.

Discovering the roles of astrocytes may unravel long-standing enigmas. Neuroscientists realized how brain chemistry shifts during stress, sleep, or attention, but their mechanisms were elusive. Now we understand that astrocytes are at the heart of these brain state changes. Shifts in attention and focus – and attention disorders – could be partly astrocytic. As Guttenplan points out, “In some conditions, things like focus and attention get disrupted… Astrocytes may be the key.” Likewise, depression, schizophrenia, or anxiety could involve dysfunction of astrocytes along with that of neurons. Indeed, the Science News article highlights that this research “opens [s] new possibilities for therapies aimed at mental illnesses such as depression and schizophrenia.” Through targeting astrocyte pathways, subsequent treatments may more specifically modulate brain circuits.

• Rethinking drugs: If astrocytes transmit neuromodulators, drugs acting on neurotransmitter quantities (such as dopamine or serotonin-based drugs) will in turn, influence astrocyte function. This knowledge may account for why some medications are effective (or not) and direct better therapies.
• Brain diseases: Astrocytes play a role in brain damage and disease (e.g., Alzheimer’s, Parkinson’s). An improved understanding of their signaling may lead to protective or restorative approaches.
• Plasticity and memory: Silent synapses (unused pathways) are considered to be responsible for learning. Astrocytes could be involved in activating such synapses or stabilizing memories. The fly and mouse research suggests that astrocytes assist the brain in adding new circuits (such as the invisible pool of synapses) without interfering with established ones.
• Attention and focus: Basic research such as this in model systems can inform human brain physiology. If astrocytes regulate arousal and “filter out the noise,” they might be key to making sense of ADHD or the impact of stress on cognition.

The takeaway at the big-picture level is that astrocytes are not passive observers. Any given astrocyte, with its extended reach, has the potential to impact neighborhoods of neurons wholesale. As Papouin wisecracks, “Textbooks say that all brain things are about neurons. One gets the impression that a great deal of brain wiring and activity is likely to be orchestrated by astrocytes.” Indeed, omitting astrocytes might have been an elementary error. Glial pioneer Ben Barres famously cautioned, “Ignoring the astrocyte is always a mistake.

Figure: A stylized brain network. New experiments and imaging (see above) are showing that astrocytes (green) thread their way through this neural mesh, actively transmitting chemical signals. Far from support cells, astrocytes get to decide how brain circuits fire under various states.

Looking Forward: The Future of Astrocyte Research

The astrocyte tale has just started. As Eroglu points out, “Understanding why brains evolved to have this layer of astrocyte control is a big question… There is something really beautiful here that remains to be understood.” More research in the future will investigate how many neural processes use astrocyte intermediaries. It will also determine if the same mechanisms are present in humans. So far, the fact that these astrocyte pathways appear conserved from flies to fish to mice suggests they are evolutionarily ancient.

In the years ahead, researchers will probably discover additional astrocyte-mediated circuits. Already, similar research has associated astrocytes with reward and motivational systems (addictive behaviors) and regulating brain blood flow. Each discovery adds another piece to the puzzle of the mind. For fans of neuroscience, the message is this: the brain’s quiet cells are not quiet and aren’t simple.

Key Takeaways: Once ignored, star-shaped brain cells, astrocytes, play an active role in shaping brain activity.

• While neurons do not fire electrical spikes, astrocytes do not, but they sense brain chemicals and react with calcium waves and transmitter release.
• New research (in flies, fish, and mice) indicates astrocytes can “gate” neuromodulators – activating in response to signals such as tyramine or norepinephrine, then modulating neurons through ATP/adenosine.
• Since astrocytes contact enormous numbers of synapses, this introduces an additional level to brain circuits, influencing learning, behavior, and mood.
• These findings create new avenues for neuroscience research and treatment: drugs could be directed toward astrocytes, and attentional disorders, depression or neurodegenerative diseases could be caused by dysfunction of astrocytes.