Astrocytes: The Unsung Heroes of Stress Management

A fresh discovery from UC San Francisco researchers indicates a new brain circuit that incorporates astrocytes, a lesser-studied type of brain cell. These cells significantly influence overactive neurons, helping modulate attention and perception. The study establishes that the neurotransmitter noradrenaline communicates with astrocytes to control overactive neurons. This process aids the brain in a smooth transition between alertness and relaxation states, presenting potential for new insights into treatments for attention disorders like ADHD.

Navigating Stress with Little-Known Brain Cells

Imagine facing an overflowing email inbox on a Monday morning, causing your head to spin. A moment of pause brings a calm, enabling you to methodically address each email. This calming effect is due to a newly recognized brain circuit involving an underappreciated type of brain cell, the astrocyte. Researchers from UC San Francisco have found that astrocytes manage communication between overactive neurons.

This fresh brain circuit, documented in a recent issue of Nature Neuroscience, assists in adjusting attention and perception. It might offer a new avenue for managing attention disorders like ADHD, which despite ample research, remain misunderstood and inadequately treated.

The study highlights that noradrenaline, a neurotransmitter equivalent to adrenaline for the brain, sends distinct messages to neurons and astrocytes: it alerts the former while instructing the latter to moderate overactive neurons.

“When you’re caught off guard or overwhelmed, your brain is so active that it can’t process more information,” explains Kira Poskanzer, Ph.D., assistant professor of biochemistry and biophysics, and senior author of the study.

Previously, it was assumed that brain activity gradually subsided over time as noradrenaline levels in the brain dwindled.

“In reality, astrocytes serve as brakes, guiding the brain towards a more relaxed state,” asserts Poskanzer.

Filling in the Gaps

Astrocytes, star-shaped cells intertwined within a grid-like pattern between the brain’s neurons, are optimally positioned to monitor and regulate neuron signals due to their multiple star-like extensions that connect to thousands of synapses.

While traditionally regarded as mere support cells for neurons, recent studies suggest that astrocytes, responsive to numerous neurotransmitters, could be crucial in neurological conditions like Alzheimer’s disease.

Michael Reitman, Ph.D., the paper’s first author and a graduate student in Poskanzer’s lab, pursued the question of whether astrocytes could explain the brain’s recovery from a surge of noradrenaline.

He said, “We were trying to solve the puzzle of how our brains bounce back from acute stress. We considered astrocytes, being sensitive to noradrenaline and located close to neurons, as potential coordinators of neuron activity.”

The Perception Gatekeepers

The research team aimed to understand perception or the processing of sensory experiences, which can significantly vary based on an individual’s state at a given time.

Poskanzer explains this with an example: the sound of thunder may seem soothing while you’re indoors and might even be ignored. However, the same sound while on a hike could make your brain more alert and safety-conscious.

The team explored how brain processing differs under varying circumstances.

The Puzzle Completed

Poskanzer and Reitman investigated how mice reacted to a drug that stimulates the same receptors that respond to noradrenaline. They observed the dilation of the mice’s pupils and studied brain signals in the visual cortex.

Surprisingly, instead of agitating the mice, the drug relaxed them. Poskanzer comments, “This result challenged our current models, leading us to consider the importance of another cell type. As it turns out, neurons and astrocytes are tied together in a feedback circuit. Considering how many neurons each astrocyte can influence, this system positions them as significant and nuanced regulators of our perception.”

The team hypothesizes that astrocytes might perform a similar role for other neurotransmitters in the brain, since transitioning smoothly between different brain states is crucial for survival.

Poskanzer concludes, “This cycle, unexpected initially, now seems quite logical. It’s simply elegant.”

Reference: “Norepinephrine links astrocytic activity to regulation of cortical state” by Michael E. Reitman, Vincent Tse, Xuelong Mi, Drew D. Willoughby, Alba Peinado, Alexander Aivazidis, Bat-Erdene Myagmar, Paul C. Simpson, Omer A. Bayraktar, Guoqiang Yu, and Kira E. Poskanzer, 30 March 2023, Nature Neuroscience.
DOI: 10.1038/s41593-023-01284-w

Funding for the study was provided by the National Institutes of Health and the National Science Foundation.

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