How can an adult brain maintain memory?

KAIST announced that the mechanism for adult brains to maintain memory has been revealed by a joint team led by Professor Jeong Won-seok of the Department of Life Science with researchers Lee Joon-hyuk’s Ph.D., Park Hyung-joo and Kim Ji-young of the Korea Institute of Brain Research. The study was recently published in “Nature.”

In adult hippocampus, conventional synapses disappear during learning and memory formation and a synaptic reconstruction occurs where new synapses occur. However, it remains unknown how synapses disappear and what role these denotes play during the learning and memory processes.

Astrocyte - Wikipedia
Astrocytes (by wikipedia)

The joint research team referred to Professor Jung Won-seok’s preceding study (Nature), in 2013 that “astrocyte,” the largest number of neuroglia that plays various roles in the central nervous system, is eliminating synapses during brain development. The study results showed that astrocyte constantly eliminates unnecessary synapses even in the adult brain and demonstrated that this phenomenon enables circuit maintenance of intramural excitatory synapses that are important for learning and memory.

The research team has developed a virus-based synaptic predatory reporter that expresses fluorescent protein combinations (mCherry and eGFP materials) that can detect acidification in synapses. Using the newly developed method, the team found that astrocyte consistently removes synapses from adult hippocampus, especially more excitatory synapses.

The research team confirmed that astrocyte is taking the initiative in removing excitatory synapses from normal hippocampus rather than the microglia cell, which is called the brain’s immune cell, reversing the conventional theory that microglia cells are the main cells to remove synapses.

When the microglia cell is artificially removed, the number of synapses does not change. However, it was observed that abnormal synapses were excessively proliferated and the function and memory-forming ability of normal hippocampus neural circuits was reduced when the hippocampus’ astrocyte was genetically engineered to prevent them from eating synapses.

Furthermore, the researchers found problems with intra-marine synaptic plasticity and memory formation in mice that inhibited astrocyte’s de-synaptic action through genetic modification. This means that the normal learning and memory of the brain cannot be maintained unless astrocyte removes unnecessary synapses.

This study suggested that the stimulating synaptic reconstruction of the adult brain by astrocyte is an essential mechanism for maintaining normal neural circuits and forming memories. This mechanism is expected to be used in a variety of studies in the future on maintaining the constancy of brain functions and associated neural circuits.

Reference: Lee, JH., Kim, Jy., Noh, S. et al. Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis. Nature (2020).

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