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In the orchestra of the brain, the activation of each neuron is controlled by two notes – excitatory and inhibitory – that come from two distinct forms of a cellular structure called synapses. Synapses are essentially the connections between neurons, which transmit information from one cell to another. Synaptic harmonies come together to create the most exquisite music, at least most of the time.
When music becomes discordant and a person is diagnosed with brain disease, scientists typically look at the synapses between neurons to determine what went wrong. But a new study by neuroscientists at Duke University suggests that it would be more useful to look at the conductor in white gloves: the astrocyte.
Astrocytes are star-shaped cells that form the glue-like structure of the brain. They are a type of cell called glia, which in Greek means “glue”. Previously discovered to be involved in the control of excitatory synapses, a team of Duke scientists also found that astrocytes are involved in regulating inhibitory synapses by binding to neurons through an adhesion molecule called NrCAM. The astrocytes reach thin, thin tentacles at the inhibitory synapse and when they touch each other, the adhesion is formed by NrCAM. Their findings were published in Nature November 11th.
“We really found that astrocytes are the conductors that orchestrate the notes that make up the music of the brain,” said Scott Soderling, PhD, chair of the Department of Cell Biology at the School of Medicine and senior author of the paper.
It was previously thought that excitatory synapses – the accelerator of the brain – and inhibitory synapses – brakes in the brain were the brain’s most important tools. Too much arousal can lead to epilepsy, too much inhibition can lead to schizophrenia, and an imbalance in either case can lead to autism.
However, this study shows that astrocytes are leading the show in overall brain function and could be important targets for brain therapies, said co-senior author Cagla Eroglu, PhD, associate professor of cell biology and neurobiology at the School of Medicines. Eroglu is a world expert on astrocytes and her lab discovered how astrocytes send their tentacles and connect to synapses in 2017.
“Most of the time, studies investigating the molecular aspects of brain development and disease either study gene function or molecular function in neurons, or consider neurons to be only the primary cells that are affected,” Eroglu said. ‘However, here we were able to show that by simply changing the interaction between astrocytes and neurons – in particular by manipulating astrocytes – we were able to dramatically alter the wiring of neurons as well.’
Soderling and Eroglu often collaborate scientifically and worked out the plan for the project with coffee and pastries. The plan was to apply a proteomic method developed in Soderling’s laboratory which was further developed by his postdoctoral associate Tetsuya Takano, who is the lead author of the article.
Takano designed a new method that allowed scientists to use a virus to insert an enzyme into a mouse’s brain that tagged proteins that connect astrocytes and neurons. Once tagged with this label, scientists could take the tagged proteins from brain tissue and use Duke’s mass spectrometry facility to identify the NrCAM adhesion molecule.
Then, Takano partnered with Katie Baldwin, a postdoctoral associate in Eroglu’s lab, to perform analyzes to determine how the adhesion molecule NrCAM plays a role in the connection between astrocytes and inhibitory synapses. Together, the labs found that NrCAM was a missing link that controlled how astrocytes affect inhibitory synapses, showing that they affect all “notes” in the brain.
“We have been very lucky to have really collaborative team members,” said Eroglu. “They worked very hard and were open to crazy ideas. I would call it a crazy idea.”
The project was funded by the NIH BRAIN Initiative, National Institute on Drug Abuse, Kahn Neurotechnology Award, Uehara Memorial Foundation, and Japan Society for the Promotion of Science.
Source of the story:
Materials provided by Duke University. Original written by Lindsay Key. Note: The content can be changed by style and length.
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