Glial cells gnawing at synapses can enhance learning and memory

Researchers at Tohoku University in Japan have shown that Bergmann glial cells (astrocytes in the cerebellum) "eat" neighboring neuronal elements
in healthy living brain tissue.

Syses — the structures in which neurons transmit signals to each other — are often pruned during brain development to improve efficiency
.
This is thought to cause various brain diseases
.

The findings, published in Nature Neuroscience, enhanced synapse phagocytosis by Bergman glia, an important area
of the brain responsible for learning, during motor learning in the mouse cerebellum.
In addition, drugs that block this phagocytosis inhibit changes in synaptic structure, leading to the loss
of part of the learning and memory process.

Glial cells, non-neuronal cells that make up half of the brain, were previously thought to be like glue — just filling in the gaps
between neurons.
However, recent studies have shown that glial cells encode information
in their unique way.

"Of course, glial cells are not another subclass of neurons," said Professor Ko Matsui of the Supernetwork Brain Physiology Laboratory at Tohoku University in Japan, who led the study
.
"We have not yet found an effect
of glia on information processing.
"

When cells engulf neighboring cells to remove debris and pathogens, it is called phagocytosis
.
The phagocytosis of microglia (immune cells in the brain) in damaged and diseased brain tissue has long been recognized
.
Recent reports have confirmed that astrocytes and microglia phagocytose neuronal elements, including synapses
during neural network remodeling in early brain development or in diseased brains.
Tracking engulfed substances in a healthy brain is a challenge because lysosomes in glia rapidly degrade
proteins.

Matsui and his team turned to the denaturing-resistant fluorescent protein pHRed to alleviate this problem
.
Using high-resolution 3D electron microscopy, they captured Bergman
glial cells gnawing at synaptic and other neuronal parts in the brains of healthy adult mice.
In addition, glial phagocytosis of brain tissue is enhanced
after cerebellum-dependent motor learning tasks.
When phagocytosis is blocked by pharmacology, some learning is lost
.

"Our findings provide a new glial mechanism
that connects learning and memory in synaptic plasticity.
In a particular state of our mind, the phagocytosis of glia may be variable, and glia may play a key role in metaplasticity in memory formation," Matsui said
.

Lead researcher Dr.
Yosuke Morizawa said their findings could help explain why people with depression, schizophrenia and Alzheimer's experience synaptic atrophy and loss
.

The team's next step is to see if glial phagocytosis at synapses in animal models of these diseases is malfunctioning
.
"A therapeutic strategy that targets glial phagocytosis may enhance memory and treat certain brain disorders," Matsui added
.

Synaptic pruning through glial synapse engulfment during motor learning