LA JOLLA (December 17, 2025)—Young minds are easily molded. Each new experience rewires a child's brain circuitry, adding and removing synaptic connections between neurons. These wiring patterns become more stable with age, but biology has left some wiggle room to ensure that adult brains can still adapt and refine their circuitry as needed. This flexibility is called neuroplasticity, and our ability to learn, make new memories, and recover from injury all depend on it.
So how does your brain know how flexible to be at different points in life? Could we target these mechanisms to open up new periods of plasticity in adulthood or use them to treat brain injuries, diseases, and disorders? What cells, genes, and molecules control the stability of your neural circuits?
Scientists at the Salk Institute have now discovered a molecule that is critical for stabilizing brain circuits in adulthood, and its source may be surprising to some. The protein, called CCN1, is secreted by star-shaped cells called astrocytes. These non-neuronal brain cells were previously seen as passive support cells, but newer research has shown they play an important role in shaping brain circuitry—and could be the missing link to treating many neurological conditions.
The CCN1 pathway could now be a prime target for new therapeutics designed to support learning and plasticity in conditions like Alzheimer's disease, depression, or post-traumatic stress disorder (PTSD) or to promote neural repair after injury or stroke.
"This study establishes the crucial role of astrocytes in actively stabilizing the connectivity of neuronal circuits," says senior author Nicola Allen , PhD, professor, holder of the Roger Guillemin Chair, and co-director of the NOMIS Foundation-funded Neuroimmunology Initiative at Salk. "Our findings demonstrate how the stability of sensory circuits is actively maintained in the adult brain. The discovery of CCN1 as a critical regulator of neuroplasticity could now inform the development of new therapeutics for brain injury and stroke, which has already been associated with CCN1 upregulation."
The study was published in Nature on December 17, 2025, and was funded by both federal research grants from the National Institutes of Health and private philanthropy.
What we know about plasticity and astrocytes
Astrocytes belong to a family of non-neuronal cells called glia, alongside oligodendrocytes, microglia, and other specialized glial subtypes. Although lesser known, these glial cells are as abundant as neurons in the central nervous system, and Allen has championed a movement in neuroscience to prioritize these cells in research. This pivot toward non-neuronal brain cells was fundamental to Salk's Year of Alzheimer's Disease Research throughout 2025, during which Allen felt especially empowered to uncover how astrocytes touch Alzheimer's, among other diseases and disorders.
Recent studies by Allen and others have shown that astrocytes have a strong influence over the formation, maturation, and elimination of synapses, especially during the earliest—and critical—periods of brain development. However, less is known about how astrocytes regulate other aspects of circuit stability, especially in later stages of life.
"We wanted to know how astrocytes regulate brain function across the lifespan," says Allen. "We already know they are involved in creating neuronal connections in the young brain, and we know some of those functions are reduced in aging. What was missing was an understanding of what astrocytes do during adulthood. We've now shown that the stability of neural circuits in the adult brain is regulated by astrocytes through the secretion of CCN1."
How astrocytes use CCN1 to orchestrate circuit stability
"Maintaining stable circuits is important for proper brain function, but the consequence is that neural plasticity and remodeling are repressed in the adult brain," says first author Laura Sancho, PhD, a postdoctoral researcher in Allen's lab. "We wanted to find out if and how astrocytes participate in this critical maintenance, and we found they are in fact essential."
To determine what, if any, role astrocytes play in plasticity and circuit stability, the researchers set their sights on the mouse visual cortex. This well-studied area of the brain is responsible for visual processing, and findings from this region often apply to other areas of the brain.
The researchers began by surveying which genes are expressed in astrocytes during the high-plasticity critical period of early development and the high-stability period of adulthood.
It quickly became clear that a protein called CCN1 was highly involved in promoting circuit stability in the mouse visual cortex. When the researchers boosted astrocytes' CCN1 expression during the critical period, they saw increased cellular maturation in both inhibitory neurons and oligodendrocytes, which dampened the circuits' neuroplasticity. On the other hand, when the researchers removed CCN1 from the adult brain, this led normally stable circuits to become destabilized.
While stability is important—especially with age—manipulating CCN1 levels could allow scientists to create pockets of plasticity that help recover or rebuild lost circuits after injury or trauma.
What makes CCN1 particularly suited for this job is its ability to bind to many extracellular components of many cell types, including excitatory and inhibitory neurons, oligodendrocytes, and microglia. By binding to important integrin proteins on the cell surface, CCN1 coordinates the maturation of multiple cell types to reduce the plasticity of the adult brain.
The therapeutic potential of targeting CCN1
These findings contribute to Allen's five-year project, funded by her 2024 NIH Director's Pioneer Award , which aims to pin down the relationship between extracellular proteins and brain plasticity. CCN1 is the first of these astrocyte proteins to be identified in her lab so far.
CCN1 and other astrocyte-derived proteins could prove to be instrumental for developing future therapeutics for neurological conditions wherein boosted plasticity would be advantageous. This includes various forms of brain injury or neurodegeneration, such as stroke or Alzheimer's disease, as well as stress and memory conditions such as post-traumatic stress disorder (PTSD).
Other authors include Matthew Boisvert, Trinity Eddy, Lara Labarta-Bajo, Jillybeth Burgado, Minerva Contreras, and Lisa Tatsumi of Salk, as well as Ellen Wang of UC San Diego.
The work was supported by the National Institutes of Health (1R01NS105742, DP11NS142587, 5F32EY033629, 1F99NS134205, 1F99NS1139511, P30 CA01495, P30 AG068635, R24NS092943, P01 AG073084-04), LIFE Foundation, Pew Charitable Trusts, Chan Zuckerberg Initiative, Roger Guillemin Chair, Salk Pioneer Fund Award, NASEM Ford Foundation, Hewitt-Eckhart Postdoctoral Fellowship, Salk Waitt Advanced Biophotonics Core, Salk GT3 Core, Salk Razavi Newman Integrative Genomics and Bioinformatics Core, Salk Flow Cytometry Core, Salk In Vivo Scientific Services, Howard and Maryam Newman Family Foundation, and Helmsley Trust.
About the Salk Institute for Biological Studies:
Unlocking the secrets of life itself is the driving force behind the Salk Institute. Our team of world-class, award-winning scientists pushes the boundaries of knowledge in areas such as neuroscience, cancer research, aging, immunobiology, plant biology, computational biology, and more. Founded by Jonas Salk, developer of the first safe and effective polio vaccine, the Institute is an independent, nonprofit research organization and architectural landmark: small by choice, intimate by nature, and fearless in the face of any challenge. Learn more at www.salk.edu .
