Overwhelmed? Your Astrocytes Can Help With That

Summary: New research reveals a newly discovered brain circuit involving astrocytes, a type of brain cell that tunes and moderates chatter between overactive neurons. This discovery could hold the key to treating attention disorders like ADHD, and sheds new light on how the brain processes information when it’s overloaded.

Source: UCSF

An overflowing inbox on Monday morning makes your head spin. You take a moment to catch your breath and your mind clears enough to go through 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 a new study from UC San Francisco, astrocytes tune and reduce crosstalk between overactive neurons.

This new brain circuit, described March 30, 2023 in Nature Neuroscience, plays a role in modulating attention and perception and may hold a key to treating attention disorders like ADHD that are poorly understood and poorly treated, despite from a wealth of research on the role of neurons.

The scientists discovered 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 another is sent to astrocytes to calm overactive 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 Kira Poskanzer, PhD, an assistant professor of biochemistry and biophysics and senior author of the study.

Until this study, it was assumed that brain activity simply calmed down over time as the amount of noradrenaline in the brain dissipated.

“We’ve shown that, in fact, it’s the astrocytes that pull the brakes and get the brain into a more relaxed state,” Poskanzer said.

A lost part

Astrocytes are star-shaped cells woven between brain neurons in a mesh-like pattern. Their many stellate arms connect a single astrocyte to thousands of synapses, which are the connections between neurons. This arrangement positions astrocytes to intercept 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 key roles in neurological conditions such as Alzheimer’s disease.

Michael Reitman, PhD, the paper’s first author who was a graduate student in Poskanzer’s lab when he did the research, wanted to know if astrocyte activity could explain how the brain recovers from a noradrenaline burst.

“It seemed like a central piece was missing in explaining how our brain recovers from that acute stress,” Reitman said. “There are these other cells nearby that are sensitive to noradrenaline and can help coordinate what the neurons around them are doing.”

Gatekeepers of Perception

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 indoors, the sound may seem relaxing and your brain may even tune it out. But if you hear the same sound during a walk, your brain can become more alert and focused on safety.

“These differences in our perception of a sensory stimulus occur because our brains are processing information differently based on the environment and state we’re already in,” said Poskanzer, who is also a member of the Kavli Institute for Basic Neuroscience.

Until this study, it was assumed that brain activity simply calmed down over time as the amount of noradrenaline in the brain dissipated. The image is in the public domain

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

Completing the puzzle

To do this, Poskanzer and Reitman looked at how rats responded when they were 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: instead of making the rats excited, the drug calmed them down.

“This result really didn’t make sense, given the models we have, and it led us down the path of thinking that another type of cell might be important here,” Poskanzer said.

“It turns out that these two things are tied together in a feedback loop. 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 the ability to switch 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,” Poskanzer said. “It’s so elegant.”

Authors: Additional authors on the paper include Vincent Tse, Drew D. Willoughby, Alba Peinado, Bat-Erdene Myagmar, and Paul C. Simpson, Jr. of UCSF, Xuelong Mi and Guoqiang Yu of Virginia Polytechnic Institute and State University, and Alexander Aivazidis and Omer A. Bayraktar of the Wellcome Sanger Institute.

Funding: This work was supported by grants from the National Institutes of Health (R01NS099254, R01MH121446, R01MH110504) and the National Science Foundation (grant no. 1750931 and CAREER 1942360).

About this neuroscience research news

Author: Robin Marks
Source: UCSF
Contact: Robin Marks – UCSF
Image: Image is in the public domain

Original Research: Closed Access.
“Norepinephrine links astrocytic activity to regulation of cortical state” by Kira Poskanzer et al. Nature Neuroscience

ABSTRACT

Norepinephrine links astrocytic activity to cortical state regulation

Cortical state, determined by population-level patterns of neuronal activity, determines sensory perception. While arousal-related neuromodulators—including norepinephrine (NE)—reduce cortical synchrony, how the cortex resynchronizes remains unknown.

Furthermore, the general mechanisms that regulate cortical synchrony in the waking state are poorly understood. Using in vivo imaging and electrophysiology in mouse visual cortex, we describe a critical role for cortical astrocytes in circuit resynchronization.

We characterize astrocyte calcium responses to changes in behavioral arousal and NE, and show that astrocytes signal when arousal-driven neuronal activity is reduced and bihemispheric cortical synchrony is enhanced. Using in vivo pharmacology, we reveal a paradoxical, synchronizing response to Adra1a receptor stimulation.

We reconcile these results by demonstrating that astrocyte-specific deletion of Adra1a increases arousal-driven neuronal activity while impairing arousal-related cortical synchrony.

Our findings indicate that astrocytic NE signaling acts as a distinct neuromodulatory pathway, regulating cortical state and linking arousal-related desynchrony with resynchronization of cortical circuitry.