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Neuroscientists identify astrocytes as the master “conductor” of the brain

In a brain orchestra, the firing of each neuron is controlled by two notes (excitatory and inhibitory) that derive from two different forms of cellular structure called synapses. Synapses are essentially connections between neurons that transmit information from one cell to another. Synaptic harmonies come together to create the most exquisite music, at least in most cases.

When music becomes dissonant and a person is diagnosed with a brain disorder, scientists usually look at synapses between neurons to determine what went wrong. However, a new study by neuroscientists at Duke University suggests that it is more useful to examine the astrocytes, the orchestra’s white-gloved conductor.

Astrocytes are star-shaped cells that form an adhesive-like framework for the brain. They are a type of cell called glia, which means “glue” in Greek. A team of Duke scientists previously found to be involved in the regulation of excitatory synapses has been involved in the regulation of inhibitory synapses by binding astrocytes to neurons via adhesion molecules called NrCAM. I also found that there was. Astrocytes extend thin, thin tentacles to inhibitory synapses, and when they touch, NrCAM forms an bond.Their findings are Nature Nov. 11.

We actually discovered that astrocytes are the conductors that regulate the notes that make up the music of the brain. “

Dr. Scott Soderling, Chair of the Department of Cell Biology, School of Medicine and Lead Author of the Paper

Excitatory synapses (accelerators of the brain) and inhibitory synapses (brake of the brain) were previously thought to be the most important devices in the brain. Too much excitement can lead to epilepsy, too much suppression can lead to schizophrenia, and both methods can lead to autism.

However, this study shows that astrocytes perform shows in overall brain function and may be an important target for brain therapy, cell biology and neurobiology in the Faculty of Medicine. Dr. Cagla Eroglu, an associate professor of science, said. Eroglu is a global astrocyte expert, and her lab discovered in 2017 how astrocytes send tentacles to connect to synapses.

“Often, studies investigating the molecular aspects of brain development and disease study the genetic or molecular function of neurons, or only consider them to be the primary cells affected,” Eroglu said. Mr. says. “But here we were able to show that simply changing the interaction between astrocytes and neurons, especially by manipulating astrocytes, can dramatically change the wiring of neurons.”

Soderling and Eroglu often collaborated scientifically, and they hashed project plans for coffee and pastries. The plan was to apply a proteomics method developed in Soderling’s laboratory, further developed by postdoctoral fellow Tetsuya Takano, the lead author of the paper.

Takano has designed a new way for scientists to use viruses to insert enzymes into the mouse brain that label proteins that connect astrocytes to neurons. When tagged with this label, scientists can remove the tagged protein from brain tissue and use Duke’s mass spectrometry to identify the adhesion molecule NrCAM.

Next, Takano collaborated with Eroglu’s lab postdoc Katie Baldwin to perform an assay to determine how the adhesion molecule NrCAM plays a role in the relationship between astrocytes and inhibitory synapses. did. Together, the lab discovered that the missing link that controls how astrocytes affect inhibitory synapses is NrCAM, and showed that they affect all “notes” in the brain. It was.

“I was very fortunate to have a really supportive team member,” Erogle said. “They worked very hard and accepted the crazy idea. I call this a crazy idea.”

This project was funded by the NIH BRAIN Initiative, the National Institute of Substance Abuse, the Khan Neuro Technology Award, the Uehara Memorial Foundation, and the Japan Society for the Promotion of Science.


Journal reference:

Toru Takano, et al. (2020) Chemogenetic discovery of astrocyte regulation of inhibition in vivo. Nature.

Neuroscientists identify astrocytes as the master “conductor” of the brain

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