Astrocytes display unique activity patterns

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Summary: Astrocytes may play an important role in information processing and memory, according to a new study.

Source: OIST

The way people experience the world is due to complex and intricate interactions between neurons in the brain.

However, a study, published on February 9, 2022 in Scientists progresssuggests that astrocytes, star-shaped non-neuronal brain cells, may also play an important role in information processing, and possibly even memory.

Using advanced imaging and analysis techniques, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) recorded signaling in single astrocytes at a level of detail and speed never seen before. in the brains of awake mice.

Their findings, including lightning-fast signals comparable to those seen in neurons and patterns of signaling activity that correspond to different behaviors, suggest that astrocytes may play crucial roles in many functions of our brain, including the way we think, move and learn. .

“If these implications are true, it will fundamentally transform the way we think about neuroscience and how the brain works,” said first author Dr. Leonidas Georgiou, a former Ph.D. student in the Optical Neuroimaging Unit at the OIST.

When we imagine our brain, we usually imagine a messy tangle of long, threadlike neurons sending electrical signals to each other in different regions of the brain. But neurons make up only half of our brain cells. Crammed into all the remaining space between the jumble of neurons are many other types of brain cells, including astrocytes.

“Compared to neurons, astrocytes have received very little attention. Astrocytes were thought to be just helper cells, supplying neurons with nutrients and removing their waste products,” said Professor Bernd Kuhn, lead author and head of the Optical Neuroimaging Unit.

But in recent years there has been growing evidence that astrocytes can listen to chemical messages sent between neurons at synapses and can respond with their own signals, providing an additional layer of complexity to how our brain receives and responds to information.

Yet signals previously detected in astrocytes were about ten times slower than signals seen in neurons, so scientists believe the cells were too slow to process information.

However, by developing a new toolkit that allows the study of astrocyte activity in awake mice in unprecedented detail, OIST researchers have shown for the first time that astrocytes generate signals in vivo as fast as those of neurons, lasting less than 300 milliseconds. .

Their toolbox was based on a new discovery: that a virus regularly used for gene therapy could “jump” from neurons to connected astrocytes. The scientists used an adeno-associated virus that contained a gene that makes infected cells fluoresce. Fluorescence increases in intensity in the presence of calcium, an important indicator of signal activity in living cells.

Once tagged, the research team was able to use a powerful homemade microscope to locate and image a single astrocyte, over multiple days for up to an hour at a time, while the mouse was awake and moving.

The scientists then used an advanced computer program to analyze the recorded images, allowing them to detect the never-before-seen ultra-fast flashes of calcium signals and to assess the signal patterns unbiased.

They found that sensory stimulation, by tickling the whiskers, resulted in very little calcium signaling, while certain behaviors, such as running or walking, resulted in high activity levels.

The scientists also realized that there were certain areas of the astrocyte, or hotspots, where activity levels were higher.

Astrocytes (meaning “stellate cells”) have a unique morphology. While the internal structure resembles a star, tiny protrusions from the cell form a cloud-like region that surrounds all nearby synapses – the junctions where different neurons meet and communicate. In mice, astrocytes are estimated to contact and take care of approximately 300,000 synapses. Credit: OIST

“These hotspot maps are like fingerprints – for a specific behavior they are stable over time, remaining the same over a period of days, and unique to each astrocyte,” Dr Georgiou said.

Even more surprisingly, the team noticed that different behaviors corresponded to unique hotspot patterns.

“So when the mouse is resting, you see a pattern. And then when the mouse is running, you see a different pattern,” Prof Kuhn said.

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It shows a man surrounded by question marks

One hypothesis suggested by Professor Kuhn is that these hotspot maps could represent memory engrams, a pattern that represents a specific behavior or memory. Different neural networks are active during specific behaviors or when learning and recalling information, which could also alter the activity of nearby astrocytes. Memory engrams are still theoretical and highly controversial, he acknowledged.

“We still don’t know how memories are stored in a brain, but it’s amazing to think that it could involve astrocytes,” he said. “It’s probably too good to be true, but it’s an exciting hypothesis to follow.”

About this neuroscience research news

Author: Press office
Source: OIST
Contact: Press office – OIST
Picture: Image is credited to OIST

Original research: Free access.
Ca+ activity maps of astrocytes labeled by axoastrocytic AAV transfer” by Leonidas Georgiou et al. Scientists progress


Abstract

Ca+ activity maps of astrocytes labeled by axoastrocytic AAV transfer

Astrocytes exhibit localized Ca2+ Microdomain (MD) activity is thought to be actively involved in information processing in the brain. However, the functional organization of Ca2+ MDs in space and time in relation to behavior and neural activity are poorly understood.

Here, we first show that adeno-associated virus (AAV) particles are anterogradely transferred from axons to astrocytes. Then we use this axoastrocytic AAV transfer to express genetically encoded Ca2+ indicators to the high contrast circuit specifically. In combination with two-photon microscopy and unbiased event-based analysis, we studied cortical astrocytes embedded in the thalamocortical vibrissal circuit.

We found a wide range of Ca2+ MD signals, some of which were ultra-fast (≤300ms). The frequency and size of signals were significantly increased by locomotion, but only subtly with sensory stimulation. Overlaying these signals gave rise to behavior-dependent maps with the characteristic Ca2+ hotspots of activity, possibly representing memory engrams.

These functional subdomains are stable over time, suggesting subcellular specialization.


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