Summary: The release of potassium ions by neurons charges the electrical activity of astrocytes, allowing the control of neurotransmission. Astrocyte-neuron crosstalk raises questions about how the interaction works in brain pathology and the implications for memory and learning.
Source: Tufts University
Researchers at Tufts University School of Medicine have discovered a previously unknown function performed by a type of cell that comprises nearly half of all brain cells.
Scientists say this discovery in mice of a new function by cells called astrocytes opens up a whole new direction for neuroscience research that could one day lead to treatments for many disorders ranging from epilepsy to Alzheimer’s disease. Alzheimer’s to Traumatic Brain Injury.
It comes down to how astrocytes interact with neurons, which are fundamental cells of the brain and nervous system that receive information from the outside world. Through a complex set of electrical and chemical signals, neurons transmit information between different areas of the brain and between the brain and the rest of the nervous system.
Until now, scientists thought that astrocytes were important, but less involved in this activity. Astrocytes guide the growth of axons, the long, thin projection of a neuron that conducts electrical impulses. They also control neurotransmitters, chemicals that allow the transfer of electrical signals in the brain and nervous system. Additionally, astrocytes build the blood-brain barrier and respond to injury.
But they didn’t seem to be electrically active like the most important neurons – until now.
“The electrical activity of astrocytes alters the functioning of neurons,” says Chris Dulla, associate professor of neuroscience in the School of Medicine and Graduate School of Biomedical Sciences, and corresponding author of a paper published today by Natural neuroscience.
“We have discovered a new way in which two of the most important cells in the brain talk to each other. Because there are so many unknowns about how the brain works, uncovering new fundamental processes that control brain function is key to developing new treatments for neurological diseases.
In addition to Dulla and lead author Moritz Armbruster, other study authors include Saptarnab Naskar, Mary Sommer, Elliot Kim, and Philip G. Haydon of Tufts University School of Medicine; Jacqueline P. Garcia of the Cellular, Molecular, and Developmental Biology Program at Tufts Graduate School of Biomedical Sciences; and researchers from other institutions.
To make this discovery, the team used brand new technology to design a technique that allows them to see and study the electrical properties of brain cell interactions, which previously could not be observed.
“With these new tools, we’ve essentially discovered completely new aspects of biology,” says Armbruster, assistant research professor of neuroscience in the School of Medicine. “As better tools arrive – for example, new fluorescent sensors are constantly being developed – we will have a better understanding of things we hadn’t even thought of before.”
“The new technology represents electrical activity with light,” says Dulla. “Neurons are very electrically active, and new technology allows us to see that astrocytes are also electrically active.”
Dulla describes astrocytes as “making sure everything is copacetic in the brain, and if something is wrong, if there’s an injury or a viral infection, they pick it up, try to react, and then try to protect the brain against insults. What we want to do next is determine how astrocytes change when these insults occur.
Neuron-to-neuron communication occurs through the release of packets of chemicals called neurotransmitters. Scientists knew that astrocytes control neurotransmitters, helping to ensure that neurons stay healthy and active. But the new study reveals that neurons also release potassium ions, which alter the electrical activity of the astrocyte and the way it controls neurotransmitters.
“So the neuron controls what the astrocyte is doing, and they communicate back and forth. Neurons and astrocytes communicate with each other in a way that was previously unknown,” he says.
The impact on future research
The discovery of astrocyte-neuron crosstalk raises many questions about how interactions function in brain pathology and in the development of learning and memory. “It makes us rethink everything astrocytes do and how the fact that astrocytes are electrically active can influence a wide range of neurological diseases,” he says.
For example, in Alzheimer’s disease, astrocytes don’t control neurotransmitters, even though that’s their basic job, Dulla explains. Similar problems occur with traumatic brain injury and epilepsy. For years, scientists thought the problem might be caused by a missing protein or a mutation that prevents a protein from working.
“Extracellular potassium accumulation in the brain has been hypothesized to contribute to the pathologies of epilepsy and migraine,” says Armbruster. “This new study allows us to better understand how astrocytes eliminate this buildup and help maintain a balance of arousal.”
Researchers are currently examining existing drugs to see if they can manipulate neuron-astrocyte interactions. “In doing so, can we ever help people learn faster or better? Can we repair brain damage when it occurs? Dulla asks.
The new technology used to make this discovery not only opens new ways of thinking about astrocyte activity, but it also provides new approaches for imaging activity across the brain. Previously, there was no way to image potassium activity in the brain, for example, or to study how potassium is involved in sleep, metabolism, or injury and infection in the brain.
“We give these tools to other labs so they can use the same tests and techniques to study the questions they care about,” he says. “Scientists are getting the tools to study headaches, breathing, developmental disabilities, and a wide range of different neurological diseases.”
About this neuroscience research news
Original research: Access closed.
“Neuronal activity leads to pathway-specific depolarization of peripheral astrocyte processesby Moritz Armbruster et al. Natural neuroscience
Neuronal activity leads to pathway-specific depolarization of peripheral astrocyte processes
Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity.
Astrocytic clearance of glutamate and K+ depends on the voltage, but the membrane potential of the astrocytes (Vm) is considered to be largely invariant. Accordingly, these voltage dependencies were not considered relevant to astrocyte function.
Use of genetically encoded voltage indicators to enable measurement of Vm At peripheral astrocyte processes (PAPs) in mice, we report large, rapid, focal, and pathway-specific depolarizations in PAPs during neuronal activity.
These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic transporters of glutamate.
We find that PAP depolarization inhibits glutamate clearance from astrocytes during neuronal activity, enhancing neuronal activation by glutamate.
This represents a new class of astrocyte subcellular membrane dynamics and a new form of astrocyte-neuron interaction.