Astrocytes Tamp Down Overexcited Neurons During Acute Stress



A brimming inbox on Monday morning sets your head spinning. You take a moment to breathe and your mind clears enough to survey the emails one by one. This calming effect occurs thanks to a newly discovered brain circuit involving a lesser-known type of brain cell, the astrocyte. According to new research, astrocytes tune into and moderate the chatter between overactive neurons.

This new brain circuit, described in Nature Neuroscience, plays a role in modulating attention and perception, and may hold a key to treating attention disorders like ADHD that are neither well understood nor well treated, despite an abundance of research on the role of neurons.

Scientists found that noradrenaline, a neurotransmitter that can be thought of as adrenaline for the brain, sends one chemical message to neurons to be more alert, while sending another to astrocytes to quiet down the over-active neurons.

“When you’re startled or overwhelmed, there’s so much activity going on in your brain that you can’t take in any more information,” said the senior author of the study.

Until this study, it was assumed that brain activity just quieted down with time as the amount of noradrenaline in the brain dissipated.

“We’ve shown that, in fact, it’s astrocytes pulling the handbrake and driving the brain to a more relaxed state,” the author said.

Astrocytes are star-shaped cells woven between the brain’s neurons in a grid-like pattern. Their many star arms connect a single astrocyte to thousands of synapses, which are the connections between neurons. This arrangement positions astrocytes to eavesdrop on neurons and regulate their signals.

These cells have traditionally been thought of as simple support cells for neurons, but new research in the last decade shows that astrocytes respond to a variety of neurotransmitters and may have pivotal roles in neurologic conditions like Alzheimer’s disease.

The team focused on understanding perception, or how the brain processes sensory experiences, which can be quite different depending on what state a person (or any other animal) is in at the time.

For example, if you hear thunder while cozying up indoors, the sound may seem relaxing and your brain may even tune it out. But if you hear the same sound out on a hike, your brain may become more alert and focused on safety.

“These differences in our perception of a sensory stimulus happen because our brains are processing the information differently, based on the environment and state we’re already in,” said the senior author.

“Our team is trying to understand how this processing looks different in the brain under these different circumstances,” the author said.

To do that, the team looked at how mice responded when given a drug that stimulates the same receptors that respond to noradrenaline. They then measured how much the mice’s pupils dilated and looked at brain signals in the visual cortex.

But what they found seemed counterintuitive: rather than exciting the mice, the drug relaxed them.

“This result really didn’t make sense, given the models we have, and that led us down the path of thinking that another cell type could be important here,” the author said. “It turns out that these two things are yoked together in a feedback circuit. Given how many neurons each astrocyte can talk to, this system makes them really important and nuanced regulators of our perception.”

The researchers suspect that astrocytes may play a similar role for other neurotransmitters in the brain, since being able to transition smoothly from one brain state to another is essential for survival.

“We didn’t expect the cycle to look like this, but it makes so much sense now,” the senior author said. “It’s so elegant.”

https://www.nature.com/articles/s41593-023-01284-w

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