Astrocytes communicate and regulate neurons. With them, there are massive implications for treating neurodegenerative diseases.
Neurons, with their long-reaching axons, nerve fibers that form critical connections to other neurons, are often thought of as the sole contributors to our brain’s thinking power. While neurons might be the star of the show, the brain would not be able to perform all its functions without the supporting cast of the brain: glial cells. Glial cells support neurons by regulating cell stability; forming myelin for the axons, enhancing the transmission of impulses between neurons; and providing protection. While the exact figures aren’t clear, the brain is roughly 50% neurons and 50% glial cells (1). Within glial cells, 40% are astrocytes (2). Astrocytes are star-shaped glial cells that have long-reaching feet (also known as the peripheral astrocyte processes) that connect to blood vessels and neural synapses. Astrocytes use these processes for many of their crucial functions; in particular, their processes control the blood–brain barrier, carry nutrients to the nervous tissue from the bloodstream, and maintain the extracellular ion balance between neurons.
While these processes are polarized, it was thought that astrocytes could not produce electrical impulses, unlike neurons (3). However, experiments have shown evidence of possible electrical communication between astrocytes and neurons. In 2022, Dr. Moritz Armbruster, a research assistant professor of neuroscience at Tufts University, utilized new technologies to visualize this electrical activity in rats. In particular, his lab researched a way to monitor the flow of potassium ions (K+) between neurons and the change in charge, also known as depolarization, of the astrocyte processes in response to the neurons firing (4).
They accomplished this by using a combination of proteins called genetically encoded voltage indicators (GEVIs), and computer models (5). GEVIs are specific proteins designed to change in fluorescence when the voltage within the cell changes. They are introduced into the brain with a virus vector, a modified virus that has no harmful effects on the body and safely transports a gene to the nucleus of the astrocytes (6). Once in the astrocyte, the GEVI protein will be synthesized by the cell (6). But, to measure the changes in fluorescence, a clear view through to the brain is needed. A scientist makes a cranial window on the top of the rat’s head, which has a glass cover slip over the incision. Once the cranial window is in place, techniques like two-photon microscopy can be used to measure the change in fluorescence (5).
Examples of what a cranial window looks like and how fluorescence can be measured in live mice. (2)(3)
These developments allow the researchers to monitor the depolarization of the astrocyte processes. Additionally, with the cranial window and viral vectors, the researchers can change parts of the astrocytes. For example, researchers can inhibit or overexpress the pumps that take in the excess potassium in the synapse. By altering the pump responsible for balancing the potassium concentration inside and outside of the astrocyte, the researchers found that the depolarization of the astrocyte processes was strongly influenced by the difference in K+ ion concentration (5). These K+ ions are released at the synapses when neurons fire, and K+ is at the core of what allows neurons and other cells to “communicate.” Ultimately, it was shown that astrocytes “undergo large, rapid, and focal voltage changes during neuronal activity,” which proves the dynamic role of astrocytes in brain function (5).
Dr. Armbruster’s team also used computer simulations to confirm their findings. The computer models used equations to predict the amount of K+ ions effused into the area between synapses, incorporating parameters like neuronal firing rates, how many K+ ions are released during an action potential, and how the ions spread through the extracellular space. These simulations confirmed that if concentrations of K+ ions were adequately high, there could be large depolarizations focused on the astrocyte processes right next to the synapses (5).
Visualization of how astrocytes control the concentration of neurotransmitters in synapses and help form the BBB.
Their findings led them to question the impact of astrocyte depolarization. They investigated further into another important role astrocytes play: uptake of the glutamate neurotransmitter. Glutamate is the main “excitatory neurotransmitter,” a neurotransmitter that excites a nerve cell, making it more likely that the chemical message will continue to jump from nerve cell to nerve cell (7). The Tufts researchers found that astrocyte depolarization was correlated with a decrease in glutamate uptake. This change means that there will be more glutamate present in the synaptic cleft for longer, making the neurons more easily excitable (5). Understanding how astrocytes interact with neurons and neurotransmitters is vital for everything, from neurodegenerative diseases to memory formation (3).
Seizure treatment is one area where this knowledge is particularly groundbreaking. Seizures themselves occur when neurons fire too frequently, “disrupting the brain’s normal electrical signals” (8). They are often caused by an overload of glutamate which causes excessive neuronal activity and a seizure. While seizures are usually treated by changing the balance of chemicals in the brain, the results of this study open the door to new treatments that instead focus on enhancing astrocyte function and controlling astrocyte membrane potential (3). Faulty astrocyte neurotransmitter uptake is also implicated in Alzheimer’s disease and epilepsy. If scientists can fully harness astrocyte abilities, it would allow for a healthier world where neurodegenerative diseases can be controlled easily. Currently, the Tufts researchers are looking at existing drugs to see if they can alter neuron-astrocyte communication (3). It is possible that one day, we will have the ability to learn quicker or repair brain injuries quicker by manipulating astrocyte behavior. These cells originally thought to be just the glue between neurons, might be the key to the way we change and enhance our brains.
Sources:
- Wikipedia contributors. (2024, November 20). Glia. Wikipedia. Retrieved from https://en.wikipedia.org/wiki/Glia
- Wikipedia contributors. (2025, January 11). Astrocyte. Wikipedia. Retrieved from https://en.wikipedia.org/wiki/Astrocyte
- Tufts Researchers Discover New Function Performed by Nearly Half of Brain Cells. (2022, April 28). Tufts Now. Retrieved from https://now.tufts.edu/2022/04/28/tufts-researchers-discover-new-function-performed-nearly-half-brain-cells
- Smiley, J. D. (2022, May 9). Study finds new way two of the most important brain cells “talk to each other.” Medical News Today. Retrieved from https://www.medicalnewstoday.com/articles/study-finds-new-way-two-of-the-most-important-brain-cells-talk-to-each-other
- Armbruster, M., Naskar, S., Garcia, J. P., Sommer, M., Kim, E., Adam, Y., Haydon, P. G., Boyden, E. S., Cohen, A. E., & Dulla, C. G. (2022). Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes. Nature Neuroscience, 25(5), 607–616. Retrieved from https://doi.org/10.1038/s41593-022-01049-x
- National Cancer Institute. (2025). Viral vector. Cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/viral-vector
- Cleveland Clinic. (n.d.). Glutamate. Cleveland Clinic. Retrieved from https://my.clevelandclinic.org/health/articles/22839-glutamate
- Boston Children’s Hospital. (2025). Childrenshospital.org. Retrieved from https://www.childrenshospital.org/conditions/seizures#:~:text=Seizures%20happen%20when%20brain%20cells,stroke%2C%20can%20look%20like%20seizures
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