Astrocytes have previously been shown to have a role in neurodevelopmental disorders as well as neurodegenerative diseases but little has been known about their role in regulating learning and memory until now. In a paper published recently in The Journal of Neuroscience, researchers from University of California Riverside report that when astrocytes—star-shaped cells that greatly outnumber neurons—overproduce a protein called ephrin-B1, the ability to retain memory weakens.
"We examined mouse learning behaviors and found that overproduction of this protein in astrocytes can lead to impaired retention of contextual memory and the ability to navigate in space," said Iryna Ethell, a professor of biomedical sciences in the School of Medicine, who led the research. "We think that astrocytes expressing too much of ephrin-B1 can attack neurons and remove synapses, the connections through which neurons communicate."
When Ethell and colleagues examined mouse cell behavior in a petri dish, they found astrocytes were "eating up" synapses when ephrin-B1 was overexpressed, suggesting that glial-neuronal interactions influence learning. "The overproduction of ephrin-B1 can be a novel mechanism by which unwanted synapses are removed in the healthy brain, with excessive removal leading to neurodegeneration" Ethell explained.
In the lab, the researchers artificially increased levels of ephrin-B1 in mice and then tested them for memory retention. They found that the mice could not remember a behavior they had just learned. In cell culture studies, they added neurons to astrocytes that overexpressed ephrin-B1 and were able to see synapse removal, with the astrocytes "eating up" the synapses.
"Excessive loss of synapses is a problem," Ethell said. "The hippocampus, the region of the brain associated primarily with memory, is plastic. Here, new neuronal connections are formed when we learn something new. But the hippocampus has a limited capacity; some connections need to go to 'make space' for new connections—new memories. To learn, we must first forget."