New research provides further evidence that glial cells do more than support and nourish neurons, which were traditionally said to be the cells responsible for brain functioning.
It appears that glial cells called astrocytes — so-called because they are shaped similarly to stars — play an active role in memory and learning.
This is according to a new study from the University of California (UC), Riverside.
The team found that astrocytes — which vastly outnumber neurons — can manage the limited space in the brain's hippocampus by pruning unwanted synapses, or the connections between neurons.
The hippocampus is a small but crucial part of the brain that is important for memory and learning.
In a paper that is now published in the Journal of Neuroscience, the researchers describe how they explored the mechanisms through which astrocytes regulate "hippocampal circuit remodeling during learning."
They found that when astrocytes produce too much of a protein called ephrin-B1, it causes memory problems in mice.
As senior study author Iryna M. Ethell, who is a professor of biomedical sciences in UC Riverside's School of Medicine, explains, "[O]verproduction of this protein in astrocytes can lead to impaired retention of contextual memory and the ability to navigate in space."
Neurons, glial cells, and synapses
There are two main types of cell in the brain and spinal cord: neurons; and the more abundant glial cells, which are made up of microglias, astrocytes, and oligodendrocytes.
Originally, it was thought that neurons were the active working units of the brain, and that the role of glial cells was to passively support and nurture them.
But more and more research is showing that glial cells are far from passive and play active roles in brain and nervous system development.
For instance, we know that astrocytes help to regulate the generation and function of synapses, or the spaces between the end of a neuron and the other neurons that it communicates with.
Communication is by means of chemical messengers, or neurotransmitters, to carry signals across the synapses.
The researchers note that previous studies have linked abnormal interactions between astrocytes and neurons to developmental and degenerative disorders of the brain.
Some of these studies have also found that the abnormal interactions are linked to impairments to memory and learning. However, they did not identify the underlying mechanisms.
Following their own findings, Prof. Ethell says that she and her colleagues believe that "astrocytes expressing too much of ephrin-B1 can attack neurons and remove synapses."
This type of "synapse loss" has been observed in Alzheimer's, amyotrophic lateral sclerosis, and other neurodegenerative diseases.
Astrocytes remove synapses
The researchers started studying the interaction between glial cells and neurons by examining the effect of astrocytes on mouse neurons in the laboratory. They found that when they added astrocytes that produce too much ephrin-B1 to the neurons, they "ate up" the synapses.
Removal of synapses in the brain alters the memory and learning circuits, so this finding suggests that interactions between glial cells and neurons are likely to influence memory and learning.
In order to explore this further, the scientists studied the effect in live mice. When they increased the animals' levels of ephrin-B1, they found that the animals could not remember behaviors that they had just learned.
It could be that "overproduction of ephrin-B1 can be a novel mechanism by which unwanted synapses are removed in the healthy brain," Prof. Ethell speculates.
This idea is supported by the fact that increase in ephrin-B1 production by astrocytes is often observed in traumatic brain injury.
But, "excessive removal" of synapses can cause problems and lead to neurodegeneration, continues Prof. Ethell.
Forgetting is necessary for learning
In the hippocampus — the part of the brain that is mostly concerned with memory — new synapses form as we learn new things.
And, says Prof Ethell, because of the limited amount of space in this small region, it is necessary to clear away some unwanted connections to make room for new ones as new memories form.
The balance between making new synapses and clearing away unwanted ones is maintained by increases and decreases in production of ephrin-B1 by the astrocytes.
"To learn," Prof Ethell maintains, "we must first forget." She and her colleagues are continuing their investigation of glial cells and wish to discover why only some, and not all, astrocytes remove synapses.
"What we know for sure is that targeting just neurons for study is ineffective. It's the glial cells, too, that need our attention."
Prof. Iryna M. Ethell