Star-shaped cells arrive and quietly issue a command that transforms the entire system.
At the precise moment a developing brain must settle into stability, star-shaped cells called astrocytes arrive to close the window of radical flexibility — a transition researchers at the University of Oregon have now traced to specific genes also implicated in autism and schizophrenia. The discovery, made in fruit fly larvae but grounded in biology conserved across species including our own, illuminates one of the most consequential passages in human development: the moment a brain learns, in a sense, to stop learning. What goes wrong in that passage may explain some of the deepest suffering in neurodevelopmental medicine — and what could be controlled there may one day offer new possibilities for healing and growth.
- The developing brain has a narrow window of radical flexibility, and when astrocytes fail to close it on time, the consequences — autism, schizophrenia, epilepsy, lasting social dysfunction — can be irreversible.
- Researcher Sarah Ackerman spent years watching astrocytes extend fine projections to envelop neural connections at precisely the right developmental moment, using light-controlled neurons to catch the process in real time.
- The mechanism hinges on two proteins — neuroligin and neurexin — whose binding locks neural circuits into place; disrupting this pathway kept brains plastic too long, producing visible motor abnormalities in larvae.
- Two of the genes controlling this switch are already known risk factors for autism and schizophrenia in humans, giving the fruit fly findings immediate and urgent clinical relevance.
- The tantalizing possibility of reopening plasticity in adult brains — for learning, recovery, or repair — now sits within conceptual reach, though researchers warn that any therapeutic use would demand extraordinary precision to avoid destabilizing the mature brain.
Inside the developing brain of a fruit fly larva, star-shaped cells called astrocytes arrive at exactly the right moment and begin wrapping themselves around neural connections, quietly commanding the brain to shift from radical flexibility into stable, adult-like wiring. Researchers at the University of Oregon have now identified which cells orchestrate this transition and which genes control the switch — a discovery that illuminates not just how brains mature, but what goes wrong when they don't.
Postdoctoral researcher Sarah Ackerman spent years observing astrocytes at work, using optogenetics to manipulate motor neurons in fruit fly larvae and watch how these glial cells responded. She found that astrocytes appeared at the precise developmental moment when plasticity needed to end, extending projections to envelop synaptic connections. The mechanism involved two proteins — neuroligin on the astrocyte and neurexin on the neuron — whose binding locks neural circuitry into place. Eliminating this pathway kept brains plastic too long; activating it too early closed the window prematurely. When plasticity was artificially extended, larvae developed abnormal crawling behaviors, a visible sign of disrupted motor circuitry.
The urgency of the finding lies in its human relevance. Two of the genes Ackerman identified are known susceptibility genes for autism and schizophrenia, and disrupted plasticity windows are also associated with epilepsy. All the cell types and signaling pathways she studied exist in humans. The work appeared in Nature in April 2021, from the lab of Howard Hughes Medical Institute investigator Chris Doe.
The human cost of these disruptions was made devastatingly visible by studies of children neglected in Romanian orphanages during the 1980s — infants deprived of stimulation during their most plastic developmental phase. Four out of five were unable to engage socially even into adulthood, their neural circuits for human connection never having formed.
Ackerman's research points in two directions at once: toward understanding why neurodevelopmental disorders emerge, and toward the more speculative possibility of reopening plasticity in adult brains to restore learning capacity. She cautioned, however, that any therapeutic approach would need to find a precise sweet spot — enough flexibility to enable growth, but not so much as to destabilize the mature brain. Next steps include similar studies in zebrafish. The fundamental question driving the work remains one that touches everyone: how does a brain learn to stop learning, and what happens when it doesn't?
Inside the developing brain of a fruit fly larva, something remarkable happens at precisely the right moment: star-shaped cells arrive and begin wrapping themselves around neural connections, quietly issuing a command that transforms the entire system. The brain shifts from a state of radical flexibility—where experience and learning reshape its wiring almost moment by moment—into something more fixed, more stable, more adult. Researchers at the University of Oregon have now identified exactly which cells orchestrate this transition and, more intriguingly, which genes control the switch. The discovery opens a door to understanding not just how brains mature, but what goes wrong when they don't.
The cells doing this work are called astrocytes, named for their star-like appearance under a microscope. They are glial cells, the supporting cast of the nervous system, present in vast numbers throughout the brain and spinal cord. Sarah Ackerman, a postdoctoral researcher in the UO's Institute of Neuroscience, spent years watching them work. Using optogenetics—a technique that lets scientists turn neurons on and off with light—she manipulated motor neurons in fruit fly larvae and observed how the astrocytes responded. What she found was that these star-shaped cells appeared at the precise developmental moment when plasticity needed to end, extending fine projections and enveloping the connections between neurons like a hand closing around something precious.
The mechanism turned out to involve two proteins: neuroligin, which sits on the astrocyte projections, and neurexin, a receptor on the developing neuron. When these two proteins bind to each other, they send a signal that locks the neural circuitry into place. Ackerman's experiments showed that eliminating this genetic pathway kept the brain plastic longer than it should be. Conversely, activating these proteins too early closed the window prematurely. The timing matters enormously. When plasticity was artificially extended, the larvae developed abnormal crawling behaviors—a visible sign that the brain's motor circuits had been disrupted.
What makes this discovery particularly urgent is its relevance to human development and disease. Two of the genes Ackerman identified are known susceptibility genes linked to autism and schizophrenia. The failure to properly close critical periods of plasticity is also associated with epilepsy. The research was conducted in fruit flies, but Ackerman emphasized that all the cell types and signaling pathways she studied exist in humans. The work appeared in Nature in April 2021 and was conducted in the lab of Chris Doe, a Howard Hughes Medical Institute investigator and professor of biology at the university.
The human cost of disrupted plasticity windows became starkly visible in the 1980s when researchers studied children abandoned in Romanian orphanages. Hundreds of infants had been neglected except during feeding and washing—deprived of the stimulation and interaction that normally shape a developing brain during its most plastic phase. When these children were eventually removed from the orphanage, four out of every five were unable to engage socially, even into adulthood. Their brains had failed to develop the neural circuits necessary for human connection, a deficit that no amount of later intervention could fully repair.
The implications of Ackerman's work extend in both directions. On one hand, understanding how the brain closes its critical periods could help explain why certain neurodevelopmental disorders emerge—and potentially point toward interventions. On the other hand, the research hints at something more speculative but tantalizing: if scientists could understand and control this mechanism, they might someday reopen plasticity in adult brains. An older person wanting to learn a new language or master a new skill might benefit from a temporary reopening of the brain's learning windows. But Ackerman cautioned that any therapeutic approach would require extreme precision. Any drug developed would need to find what she called "the sweet spot for plasticity"—enough flexibility to enable learning, but not so much that it disrupts the stability the mature brain needs to function.
The research is moving forward. Ackerman's team is now planning similar studies in vertebrates, specifically using zebrafish, which have been developed as a model organism for medical research at the University of Oregon since the 1970s. The path from laboratory discovery to human therapy is long and uncertain, but the fundamental question driving the work is one that touches everyone: how does a brain learn to stop learning, and what happens when it doesn't?
Citas Notables
All of the cell types and signaling pathways I looked at are present in humans. Two of the genes that I identified are susceptibility genes linked to neurodevelopmental disorders including autism and schizophrenia.— Sarah Ackerman, University of Oregon postdoctoral researcher
If we can understand that mechanism of the closing of this critical developmental period, we could possibly reopen plasticity in older people who want to, say, learn a new language or learn a new task.— Chris Doe, Howard Hughes Medical Institute investigator
La Conversación del Hearth Otra perspectiva de la historia
So these astrocytes—they're not neurons themselves. They're support cells. Why would they be the ones controlling something as fundamental as when the brain stops being plastic?
Because plasticity isn't just about the neurons. It's about the connections between them, the synapses. Astrocytes are the guardians of those synapses. They're positioned to see what's happening and respond. When the time is right developmentally, they move in and literally wrap around the connections, and through that physical contact, they send a signal: lock this down.
The neuroligin-neurexin binding—that's the actual molecular handshake that says "stop changing."
Exactly. It's a conversation between two proteins. One sits on the astrocyte, one sits on the neuron. When they bind, the neuron gets the message. And the timing is everything. Too early and the brain can't learn what it needs to learn. Too late and you get developmental disorders.
Which brings us to the human diseases. Autism and schizophrenia. Are we saying those conditions involve astrocytes not doing their job properly?
Not necessarily. The genes Ackerman identified are susceptibility genes—they increase risk. The actual biology is probably more complex. But yes, if the timing of plasticity closure is off, the developing brain doesn't wire itself correctly. And that can manifest as neurodevelopmental disorder.
And the therapeutic dream—reopening plasticity in adults. That seems almost too good to be true.
It probably is, at least for now. But the principle is sound. If you understand the mechanism that closes the window, theoretically you could open it again. The catch is precision. You can't just flood the brain with a drug that reopens plasticity everywhere. You'd create chaos. You need the sweet spot.