How astrocytes keep synchronized neuronal equipment

Key questions answered

Q: What did scientists discover about astrocytes and the coding of information?
A: The study found that astrocytes regulate GABA’s environmental levels using a protein called GAT3, which is essential to help neurons coordinate their activity and encode visual information as a group.

Q: What happened when GAT3 was removed from astrocytes?
A: When GAT3 was knocked out in the visual mice cortex, individual neurons still responded to stimuli, but their coordination of the whole weakened, which makes it difficult for the brain to represent visual entry efficiently.

Q: Why does this matter for brain disorders?
A: Interruption at GAT3 levels has been related to seizures, repetitive behaviors and motor problems; This study provides a mechanistic explanation by showing how astrocytes affect neural processing at the group level.

Summary: Astrocytes, long and eclipsed by neurons, are demonstrating vital for how the brain processes information. A new study shows that astrocytes use a protein called GAT3 to handle GABA’s environmental levels, helping neurons to work together to encode visual entry.

When the researchers knocked Gat3 in the visual mice cortex, individual neurons still worked, but their ability to act as a team collapsed, interrupting collective processing. This coordination breakdown could help explain neurological symptoms under conditions related to altered GAT3 expression.

Key facts:

GAT3 function: Astrocytes use GAT3 to regulate environmental gab and maintain neuronal balance. Disrupted coordination: Without GAT3, neuronal sets lose synchronization, affect information coding. Clinical relevance: GAT3 changes are linked to seizures, repetitive behaviors and motor dysfunction.

Source: Picower Institute at MIT

Cells called astrocytes are as abundant in the brain as neurons, but scientists have spent much less time discovering how they contribute to brain functions.

A new study by MIT researchers at the Picower Learning and Memory Institute shows that a function seems to maintain the necessary chemical conditions for neurons groups to join to encode information.

Specifically, the neuroscientists showed that when they eliminated the ability of astrocytes in the visual mice cortex to produce a protein called “Gaba Transporter 3 (GAT3)”, the neurons there became less capable as a group to represent information about laboratory laboratory films.

Gaba is a common neurotransmitter that sharpens neuronal activity and astrocytes use Gat3 to regulate GABA’s environmental level in its area.

In the study in Elife, eliminating Gat3 in the visual cortex left the neurons stewed in a soup of excess GABA that only produced subtle effects on individual neurons, but nevertheless joined a significant deterioration in their efforts as a set responsible for the visual function.

“Even if the changes at the level of a single neuron that represent a visual stimulus do not change significantly, if one hundred neurons have some small changes, that could add at the population level to a significant and significant change,” said principal author Mriganka Sur, Paul and Lilah Newton at the Picower Institute and the department of brain and cognitive sciences of MIT (BCs).

In particular, the authors wrote in Elife, this is the first study in living GAT3 mice at scales that cover individual and functional sets of hundreds of them.

To make the discovery, BCS Jiho Park’s graduate used a new implementation of the CRISPR/CAS9 gene edition to knock GAT3 combined with statistical and computational analysis of neuronal activity at the population level, South said.

Go out

As neuroscientists have studied the visual brain system for many decades, neurons have claimed most of their attention because they are electrically active and are directed more easily genetically, South said. The technology to track the activity of astrocytes and to manipulate their function has not developed so fast.

But in 2019, the National Health Institutes gave South a subsidy to develop better tools to study astrocytes. This financing helped the laboratory to create the variant of CRISPR/CAS9 that they call MRCUTs that enabled the new study. The tool allowed them to use only a viral vector to point to the gene that codifies GAT3 for multiple cuts. That multiplexed attack knocked it out decisively and precisely in the astrocytes of the visual cortex.

Once Park knocked Gat3, he could see the effects of his absence visually tracking the calcium activity of neurons, a proxy for his electrical activity. The consequences were more subtle than the team expected.

Sunk in Gaba, neurons fired less robust and less reliable. When the mice were watching only a gray screen, instead of movies, neurons would also be activated less frequently.

But to the surprise of the researchers, when Gat3 had left, the neurons individually still did their job. The cells that in the presence of GAT3 responded to different characteristics of the images that the mice were seeing, such as the orientation of the lines, they kept responding even after GAT3 was eliminated.

Although Gaba’s environmental levels were higher, neurons still shared gaba through their direct connections, or “synapse”, as before, which means that their direct dialogue with each other did not change.

“We expected to see changes in the tuning orientation, among other things, but we didn’t see that,” Park said. “That is why we analyze the deepest levels of analysis to see if there is any difference.”

Interrupted teamwork

This deepest analysis occurred at the level of broader neuronal sets, where Park used several statistical and computational methods to analyze how collective information that encodes hundreds of neurons changed when GAT3 was eliminated.

Using a statistical method called “generalized linear model” to analyze activity patterns throughout the whole, Park discovered that when Gat3 was eliminated, the activity of neurons became less predictive of the activity of others in the group compared to when GAT3 was present.

This indicated that while individual neurons could still be doing what they were supposed to be, their coordination was affected.

Meanwhile, using a decoder based on the “support vector machine” to discern the information represented by the sets, he discovered that when GAT3 was present, the decoder could improve its evaluation as more neurons were added to its sample.

But when Gat3 was knocked out, the decoder could no longer determine the information represented even as its sample size increased.

“Decoding deficits after GAT3 ablation provide evidence that environmental GABA astrocytic regulation is essential to organize coordinated neuronal activity patterns necessary for efficient coding of information in visual cortical networks,” wrote the authors in Elife.

Clinical cases

The finding that the lack of GAT3 interrupts neuronal coordination at the population level could help explain the clinical observations that the reduction of GAT3 in the thalamus increases the risk of seizures, the increase of GAT3 in the striated body contributes to repetitive behaviors and the reduction of GAT3 in the Pallidus Pallidus Pallidus coordination of globus, Park said.

“Because our study is the first to observe the effects of GAT3 on a population level, it could help link some of the behavioral phenotypes that people have been seeing,” Park said.

But more research is needed, South said, because there are other GAT proteins, such as Gat1, that the brain could use to compensate.

In addition to Park and Sur, the other authors of the newspaper are Grayson Sipe, Xin Tang, Prachi Ojha, Giselle Fernandes, Yi none Leow, Caroline Zhang, Yuma Osako, Arundhati Natesan, Gabrielle Drummond and Rudolf Jaenisch.

Financing: The National Health Institutes, a Muri subsidy, the Autism Research Initiative of the Simons Foundation, the Freedom Together Foundation and the Picower Institute for Learning and Memory provided funds for the study.

About this news of astrocytes and neurotransmission research

Author: David Orenstein
Source: Picower Institute at MIT
Contact: David Orenstein – Picower Institute at MIT
Image: The image is accredited to Neuroscience News

Original research: open access.
“Astrocytic modulation of the population coding in the visual mouse cortex through the GABA 3 transporter revealed by the edition of Crispr/Cas9 multiplexed” by Mriganka Sur et al. elegant

Abstract

Astrocytic modulation of the population coding in the visual mouse cortex through the GABA 3 transporter revealed by the edition of the multiplexed CRISPR/CAS9

Astrocytes, which are increasingly recognized as fundamental components of brain circuits that govern a wide range of functions, express Gaba Transporter 3 (GAT3), a specific GABA transporter of astrocytes responsible for the maintenance of extra synaptic GABA levels.

Here, we examine the functional paper of GAT3 in the modulation mediated by astrocytes of the neuronal activity and the coding of information.

First, we develop a multiplexed CRISPR construction applicable for the effective genetic ablation of GAT3 in the visual cortex of adult mice.

Using calcium images of two in vivo photons of the visual cortex neurons in Knockout Gat3 mice, we observe changes in the spontaneous individual neuronal response properties and visual conduction, such as the magnitudes of response and the variability of the trial to trial.

Gat3 Knockout exerted a pronounced influence on neuronal activity at the population level, altering the dynamics of response of neuronal populations and harming their ability to accurately represent the stimulus information.

These findings show that GAT3 in astrocytes deeply shares the sensory information coding capacity of neurons and networks within the visual cortex.