The brain is constantly forming and destroying synapses, keeping it efficient by storing only useful information. Researchers have now discovered the key to this process, which also plays a role in neurological disorders such as schizophrenia, autism, epilepsy and frontotemporal dementia (FTD).
Facts about the Brain
Between 50 and 90% of the brain’s gray matter is not composed of neurons but of a supporting tissue composed of several cells (astrocytes, microglia, oligodendrocytes, Schwann cells…) collectively known as glial cells. These cells have mostly a supporting function, but can also communicate with neurons through ions or neurotransmitters.
Think of the brain as though it is a growing tree: The branches grow in all directions and need to be pruned regularly so that the main branches develop in the best conditions. So from the age of three, the number of connections between neurons (synapses) decreases. An army of “gardeners” eliminates the less relevant synapses and retains the most important ones, for example, those that signal danger.
Microglia versus astrocytes
Until now, it was thought that this task was performed by microglia, which are already responsible for cleaning the cellular remains of damaged neurons (e.g. after a brain injury). In 2011, an Italian team showed how the microglia “gobbles up” synapses during postnatal development in mice. By reducing the number of microglia, the researchers found that the mice had more synapses but were less efficient.
But their role as gardeners is being questioned by a new study published in Nature. “Here we show for the first time that it is astrocytes, and not microglia, that constantly eliminate excessive and unnecessary excitatory synaptic connections in adults in response to neuronal activity,” said Won-Suk Chung, a researcher at the Korea Advanced Institute of Science and Technology (Kaist). Astrocytes, named for their star shape, form a network around neurons, like vines around a branch. They perform many functions, particularly in synaptic transmission and linking of neurons, but their ability to ingest synapses through phagocytosis was previously unknown.
Removing the unnecessary synapses is vital
To reach this conclusion, the researchers developed a molecular sensor that can detect the elimination of synapses by glial cells and quantify the frequency and type of synapses eliminated. They used this molecular sensor in mice that lack the MEGF10 gene, which enables astrocytes to eliminate synapses. These mice have an unusually high number of excitatory synapses in the hippocampus. However, these excitatory synapses are functionally impaired, which leads to faulty learning and the formation of excess memory.
Astrocytes to treat Schizophrenia and Autism
The question remains as to how good and bad synapses are resolved. Do astrocytes indiscriminately destroy synapses, and do only the most active and therefore most frequently used synapses resist their attack? It is also possible that less active synapses send out chemical signals that attract astrocytes. It also appears that each region of the brain has different synaptic elimination rates. In any case, modulation of astrocytes could be a treatment option for a variety of neurological disorders associated with synaptic malfunctions, such as some forms of autism, schizophrenia, dementia, and epilepsy.