Summary: Synaptic engulfment of Bergmann glial cells in the cerebellum was enhanced during motor learning in mice.
Source: Tohoku University
Researchers from Tohoku University have shown that Bergmann glial cells, astrocyte-like cells in the cerebellum, “eat” their neighboring neural elements in healthy living brain tissue.
Synapses – structures that allow neurons to transmit signals to each other – are regularly pruned throughout brain development to improve its efficiency. Disruption of this is thought to lead to various brain disorders.
The researchers’ findings, which were detailed in the review Natural Neurosciences, found that Bergmann’s glial engulfment of synapses was enhanced during motor learning in the mouse cerebellum, a brain region important for learning.
Moreover, the pharmacological blocking of this engulfment inhibited synaptic structural changes, resulting in the loss of part of the learning and memory process.
It was previously believed that glial cells, non-neuronal cells occupying about half of the brain, were like glue – simply filling in the space between neurons. However, recent findings show that glial cells encode information in their own way.
“Glial cells are of course not another subcategory of neurons,” says Professor Ko Matsui of Tohoku University’s Supergrid Brain Physiology Laboratory, who led the research. “We have not yet discovered the glial impact on information processing.”
When cells engulf neighboring cells to remove debris and pathogens, it is called phagocytosis. Phagocytosis by microglia, the brain’s immune cells, in damaged and diseased brain tissue has long been recognized.
Recent reports have established that astrocytes and microglia phagocytose neural elements, including synapses during early brain development or when dramatic neural network remodeling occurs in the diseased brain.
Tracing engulfed materials is difficult in healthy brains because glia lysosomes rapidly degenerate proteins.
Matsui and his team turned to the degeneration-resistant fluorescent protein pHRed to alleviate this problem. Using high-resolution 3D electron microscopy, they captured Bergmann’s glia munching on parts of synapses and other neuronal parts in healthy adult mouse brains.
Moreover, glial phagocytosis was enhanced in brain tissues collected after cerebellum-dependent motor learning tasks. When phagocytosis was pharmacologically blocked, some learning was lost.
“Our discovery provides a novel glial mechanism in synaptic plasticity linking learning and memory. It is possible that the phagocytic capacity of glia is variable according to certain states of our mind and that glia may play a central role in the meta-plasticity of memory formation,” Matsui said.
The study’s lead researcher, Dr. Yosuke Morizawa, says their findings could have possible implications for why synaptic shrinkage and loss occurs in depression, schizophrenia and Alzheimer’s disease.
The team’s next step is to see if glial phagocytosis of synapses malfunctions in animal models of these diseases.
“A therapeutic strategy designed to target glial phagocytosis could improve memory and treat certain brain disorders,” Matsui added.
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About this memory and learning research news
Author: Press office
Source: Tohoku University
Contact: Press Office – Tohoku University
Image: Image is credited to Morizawa & Matsui
Original research: Access closed.
“Synaptic pruning by engulfing glial synapses during motor learning” by Ko Matsui et al. Natural neuroscience
Summary
Synaptic pruning by engulfment of glial synapses during motor learning
Synaptic pruning is a fundamental neural circuit refinement process in learning and memory. Accumulating evidence suggests that glia participate in the sculpting of neural circuits through the engulfment of synapses.
However, it remains unclear whether glial involvement in synaptic pruning has a role in memory formation.
Using newly developed phagocytosis reporter mice and three-dimensional ultrastructural characterization, we found that synaptic engulfment by cerebellar glia of Bergmann (BG) occurs frequently during cerebellum-dependent motor learning in mice.
We observed an increase in pre- and post-synaptic nibbling by BG as well as a reduction in spine volume after learning. Pharmacological blockade of engulfment with annexin V inhibited both spinal volume reduction and nocturnal improvement in motor adaptation.
These results indicate that BG contributes to the refinement of mature cerebellar cortical circuitry through synaptic engulfment during motor learning.