Nerve glial cells – astrocytes – are involved in eating the interneuronal contacts in the hippocampus of adult mice, the study said. published In the magazine Nature… Scientists have also shown that astrocytes use the MEGF10 receptor for this. Disabling its gene in mice exhibited impairments in synaptic plasticity and memory formation.
In the adult brain, some synapses constantly replace others during new experiences or the use of cognitive functions. This happens especially often in the hippocampus – the main structure of memory formation. Moreover, the mechanism of the formation of new synapses in the hippocampus of the adult brain is quite understandable science, while removing old ones is not so simple.
The renewal of connections between neurons occurs not only in the adult brain, but also during its development. It is shown that in this are involved auxiliary brain cells – nerve glia. Microglia and astrocytes, the well-known eaters of brain cells, can phagocytose the synapses of the developing brain. The latter take up synapses via the MEGF10 and MERTK receptors, which trigger phagocytosis.
Researchers at the Korea Advanced Institute of Science and Technology led by Joon-Hyuk Lee and Ji-young Kim have suggested that astrocytes are involved in eating synapses and in the adult brain to maintain its plasticity. To do this, they used fluorescent proteins that stained cells depending on the acidity of the environment. The sequences of proteins were “sewn” into the genomes of neurons, after which the acidic environment of glial lysosomes, whose enzymes digest the eaten, was colored red. The synapse proteins were stained blue.
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Photo of excitatory synapses by fluorescence microscopy. Synaptic proteins are colored blue, and lysosomes with an acidic medium are colored red.
Lee et. al. / Nature, 2020
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-So it was possible to show that there are indeed glial lysosomes in the synapses of the hippocampus. Moreover, there were more glia lysosomes in excitatory synapses (p
The biologists decided to test whether the MEGF10 receptor is involved in the process of eating synapses and turned off its gene in astrocytes. After that, the number of lysosomes actually decreased in excitatory synapses (p ≤ 0.003), while in inhibitory synapses it remained the same (p> 0.05). This suggests that astrocytes use the MEGF10 receptor to selectively disrupt excitatory synapses. At the same time, in mice with MEGF10 turned off, there were more excitatory synapses in the hippocampus, due to which the release of neurotransmitters in them was reduced, apparently to compensate for the amount.
The researchers also tested how memory and synaptic plasticity worked in mice without MEGF10. They acted on the neurons of the hippocampus with strong stimuli in order to investigate the process in them long-term potentiation – strengthening of active synapses. Compared to controls, these neurons showed decreased synaptic plasticity. Mice without MEGF10 also performed worse in the memory test, where they had to recall previously presented objects.
So the researchers showed that astrocytes are able to phagocytose synapses in the hippocampus of adult mice using the MEGF10 receptor. This discovery will help in understanding the processes of brain plasticity while maintaining homeostasis, including memorization.
Astrocytes are able to eat not only synapses, but also dead neurons. We recently wrotethat together with microglia they share responsibilities in this process: microglia eat up the body of neurons and nearby processes, and astrocytes – distant processes of the dendritic tree.