The developing brain is constantly creating new connections of neurons called synapses as it learns and remembers. Critical connections (repeatedly introduced connections, such as ways to avoid danger) are nurtured and strengthened, and connections that are deemed unnecessary are removed. The adult brain undergoes similar pruning, but it was unclear how or why the adult brain synapses were eliminated.
A team of South Korean-based researchers has now discovered the plasticity of the adult brain and the underlying mechanisms of potentially neuropathy.They reported their findings on December 23 Nature..
“Our discoveries have profound implications for learning, memory, and understanding how neural circuits change in disease,” said Won-Suk Chung, an assistant professor at KAIST’s Department of Biological Sciences. Stated. “Changes in synaptic numbers are strongly associated with the prevalence of various neurological disorders, including autism spectrum disorders, schizophrenia, frontotemporal dementia, and some forms of seizures.”
The gray matter of the brain contains microglia and astrocytes. These are two complementary cells that specifically support neurons and synapses. Microglia are the front-line immune defenses involved in eating pathogens and dead cells, and astrocytes structure and maintain homeostasis by helping control signal transduction between neurons. It is a star-shaped cell that helps. According to Professor Chung, microglia are commonly thought to eat synapses as part of a process purification effort known as phagocytosis.
“For the first time, we have shown that it is the astrocytes, not microglia, that constantly eliminate excessive and unnecessary adult excitatory synaptic connections in response to neural activity using new tools,” said Professor Chung. .. “Our paper challenges the general consensus in this area that microglia are the major synaptic phagocytes that control the number of synapses in the brain.”
Professor Chung and his team have developed a molecular sensor that detects synaptic depletion by glial cells and quantified how often and what type of cellular synapse was depleted. They also deployed it in a mouse model without MEGF10, a gene that allows astrocytes to eliminate synapses. Adults with this defective astrocyte phagocytosis abnormally increased the number of excitatory synapses in the hippocampus. Through a collaborative study with Dr. Hyungju Park of KBRI, they showed that the increase in these excitatory synapses was functionally impaired and that MEGF10 caused defects in learning and memory formation in depleted animals.
“Through this process, we show that astrocytes are a major player in synaptic elimination, at least in the adult hippocampal CA1 region, and that astrocyte function is essential for controlling synaptic number and plasticity. “We do,” said Chung.
Professor Chung said researchers have just begun to understand how synaptic removal affects brain maturation and homeostasis. Preliminary data from his group in other brain regions suggest that each region has a different rate of synaptic deprivation by astrocytes. They believe that a variety of internal and external factors influence how astrocytes regulate each local circuit and plan to elucidate these variables.
“Our long-term goal is to understand how astrocyte-mediated synaptic turnover affects the initiation and progression of various neuropathy,” says Professor Chung. “It is interesting to assume that regulating the phagocytosis of astrocytes to restore synaptic connectivity may be a new strategy in treating a variety of brain disorders.”