Summary: New research reveals a newly discovered brain circuit involving astrocytes, a type of brain cell that chirps and moderates overactive neurons. The discovery could hold the key to treating attention disorders like ADHD, and sheds new light on how the brain processes information when overwhelmed.
A full inbox on Monday morning makes your head spin. 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 from UC San Francisco, astrocytes act as chatter between overactive neurons and moderate them.
This new brain circuit, described March 30, 2023 Nature is neuroscienceAttention and perception play a role in modulation and may hold a key to treating attention disorders such as ADHD that are not well understood or well treated, despite a wealth of research into the role of neurons.
The 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 another 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, assistant professor of biochemistry and biophysics and senior author of the study.
Until this study, it was assumed that as the amount of noradrenaline in the brain was depleted, brain function recovered.
“We showed that, in fact, it’s pulling the astrocyte handbrake and driving the brain into a more relaxed state,” Poskanzer said.
A missing piece
Astrocytes are star-shaped cells woven between neurons in the brain in a grid-like pattern. Their many stellate arms connect a single astrocyte to thousands of synapses, the connections between neurons. This arrangement positions astrocytes to listen to neurons and regulate their signals.
These cells are traditionally thought of as simple support cells for neurons, but new research in the past decade has shown that astrocytes respond to a variety of neurotransmitters and may play an important role 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 burst of noradrenaline.
“It seemed that a central piece was missing in the explanation of how our brain recovers from that acute stress,” Rittman said. “There are these other cells nearby that are sensitive to noradrenaline and can help coordinate what the neurons around them are doing.”
Gatekeeper of Perception
The team focuses 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 relaxing indoors, the sound may seem relaxing and your brain may tune it out. But if you hear the same sound while hiking, your brain may become more alert and focus 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 Fundamental Neuroscience.
“Our team is trying to understand how this processing in the brain looks different in these different situations,” he said.
Complete the puzzle
To do this, Poskanzer and Reitman watched how rats responded when given a drug that stimulated 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 appeared to be the opposite: instead of making the mice excited, the drug relaxed them.
“This result didn’t really make sense with the models we had, and it led us to think that another cell type might be important here,” Poskanzer said.
“It turns out that these two things are linked together in a feedback circuit. Given how many neurons each astrocyte can talk to, this system makes them really important and fine regulators of our perception.”
The researchers suspect that astrocytes may play a similar role for other neurotransmitters in the brain, as being able to smoothly transition from one brain state to another is essential for survival.
“We didn’t expect the cycle to look like this, but it makes a lot of sense now,” Poskanzer said. “It’s very elegant.”
Author: Additional authors of the paper include Vincent Tease, Drew D. Willoughby, Alba Peinado, Bat-Erden Myagmar, and UCSF’s Paul C. Simpson Jr., Juelong Mi and Guoqiang Yu of Virginia Polytechnic Institute and State University, and Alexander Ivazidis and Omar A. of the Wellcome Sanger Institute. of the airport.
Financing: This work was supported by grants from the National Institutes of Health (R01NS099254, R01MH121446, R01MH110504) and the National Science Foundation (Grant Nos. 1750931 and CAREER 1942360).
With this news of neuroscience research, Dr
Author: Robin Marks
Contact: Robin Marks – UCSF
Image: Image is in public domain
Original Research: Closed access.
“Norepinephrine links astrocytic activity to regulation of cortical statesBy Kira Poskanzer et al. Nature is neuroscience
Norepinephrine links astrocytic activity to regulation of cortical states
Cortical state, defined by population-level neuronal activity patterns, determines sensory perception. Although arousal-related neuromodulators – including norepinephrine (NE) – reduce cortical synchrony, how the cortex resynchronizes remains unknown.
Furthermore, the general mechanisms governing cortical synchrony during wakefulness 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 the calcium response of astrocytes to behavioral arousal and NE changes and show that astrocytes signal when arousal-driven neuronal activity decreases and bi-hemispheric cortical synchrony increases. Using in vivo pharmacology, we discover a paradoxical, synchronizing response to Adra1a receptor stimulation.
We reconcile these results by demonstrating that astrocyte-specific deletions Adra1a Enhances arousal-driven neuronal activity, while impairs arousal-related cortical synchrony.
Our findings show that astrocytic NE signaling acts as a distinct neuromodulatory pathway, regulating cortical state and linking arousal-related dyssynchrony with cortical circuit resynchronization.