Answered vital questions
Q: What did researchers learn about astrocytes and data compression?
A: The study found that astrocytes regulate ambient GABA levels using a protein called Gat3, which is essential for helping neurons coordinate their activity and encode visual information as a group.
Q: What transpired after the astrocytes removed Gat3?
A: When Gat3 was knocked out in the visual cortex of mice, individual neurons still responded to stimuli, but their ensemble coordination weakened, making it harder for the brain to represent visual input efficiently.
Q: Why does this problem for mental illnesses?
A: Disruption in Gat3 levels has been linked to seizures, repetitive behaviors, and motor problems—this study provides a mechanistic explanation by showing how astrocytes affect group-level neural processing.
Summary: Astrocytes, longer overshadowed by cells, are proving critical to how the brain processes information. A new research demonstrates that neurons collaborate to encode sensory input by enabling them to manage external GABA levels using a protein called Gat3.
Specific neurons continued to function after being knocked out by researchers in the visual brain of mice, but their ability to work together as a team deteriorated, causing shared processing to be hampered. This coordination break may help explain neurological signs in conditions linked to altered Gat3 appearance.
Important Information
- Gat3 Function: Astrocytes use Gat3 to control external GABA and maintain neuronal stability.
- Disrupted Coordination: Without Gat3, neurological bands lose alignment, impairing information processing.
- Clinical Relevance: Gat3 changes are linked to engine difficulties, repetitive behavior, and seizures.
Origin: MIT Picower Institute
Cells called astrocytes are about as plentiful in the mind as cells, but researchers have spent substantially less moment figuring out how they contribute to mental capabilities.
One work, according to a book study by MIT researchers at The Picower Institute for Learning and Memory, appears to be maintaining the chemical conditions required for groups of neurons to unite to transmit information.
In particular, the neuroscientists discovered that neurons in the visual cortex of mice became less able to represent information about the movies lab mice were seeing when they were knocked out of the ability of astrocytes to produce a protein called “GABA transporter 3 ( Gat3 ).
GABA is a common inhibitory neurotransmitter that sharpens neural activity and astrocytes uniquely use Gat3 to regulate the ambient level of GABA in their area.
In the study in eLife, knocking out Gat3 in the visual cortex left neurons stewing in a soup of excess GABA that only had subtle effects on individual neurons but still significantly impairs their capacity as an ensemble to control visual function.
According to senior author Mriganka Sur, Paul and Lilah Newton, Professor at The Picower Institute and MIT’s Department of Brain and Cognitive Sciences,” Even if the changes at the level of a single neuron representing a visual stimulus do not change significantly, if a hundred neurons have some minor changes, that could add up to a measurable, significant change at the population level.”
Notably, the authors wrote in , eLife, this is the first study in live mice of Gat3 at scales spanning individual cells and functional ensembles of hundreds of them.
According to Sur, BCS graduate student Jiho Park used a novel CRISPR/Cas9 gene editing technique to knock out Gat3. The findings were aided by statistical and computational analyses of neural activity at the population level, according to Sur.
Gat out
As neuroscientists have studied the brain’s visual system over many decades, neurons have claimed most of their attention because they are electrically active and more easily targeted genetically, Sur said. Technology for monitoring and controlling astrocyte activity hasn’t developed as quickly.
However, the National Institutes of Health awarded Sur$ 200,000 to create better astrocyte study tools. That funding helped the lab create the variant of CRISPR/Cas9 they call MRCUTS that enabled the new study. The tool made it possible for them to target the gene that encoding Gat3 for multiple cuts using just one viral vector. In visual cortex astrocytes, that multiplexed attack effectively and decisively eliminated it.
Once Park knocked out Gat3, she could see the effects of its absence by visually tracking the calcium activity of neurons, a proxy for their electrical activity. The effects were less obvious than the team had anticipated.
Neurons were awash in GABA, firing less robustly and reliably. When the mice were watching only a gray screen, instead of movies, the neurons would spontaneously activate less often, too.
However, the researchers were surprised to discover that each of the neurons could continue to function after Gat3 was removed. Cells that were in response to various aspects of the images the mice were seeing, such as the orientation of lines, remained responsive even after Gat3 was removed.
Though ambient levels of GABA were higher, pairs of neurons still shared GABA through their direct connections, or” synapses”, as before, meaning their direct dialogue with each other didn’t change.
We anticipated seeing changes to orientation tuning, among other things, but that didn’t happen, according to Park. We looked into more detailed analysis to see if there were any differences because of this.
Disrupted teamwork
When Park used a number of statistical and computational methods to examine how the collective information encoding by hundreds of neurons changed when Gat3 was knocked out, the deeper analysis took place at the level of larger neural ensembles.
When Gat3 was knocked out, the activity of neurons decreased as a result of using a statistical technique known as a” Generalized Linear Model” to compare the ensemble’s activity patterns.
This indicated that while individual neurons might still be doing what they were supposed to, their coordination was impaired.
She discovered that when Gat3 was present, the decoder could improve its assessment as more neurons were added to its sample by using a” Support Vector Machine”-based decoder to discern the information that ensembles were representing.
However, when Gat3 was removed, the decoder was unable to identify the represented information even as its sample size increased.
” The decoding deficits following Gat3 ablation provide evidence that astrocytic regulation of ambient GABA is essential for organizing the coordinated neuronal activity patterns necessary for efficient information encoding in visual cortical networks”, the authors wrote in , eLife.
Cases that are clinical
The discovery that a lack of Gat3 disrupts neural coordination at the population level might contribute to the development of the theory that, according to Park, Gat3 reduction in the globus pallidus impairs motor coordination, Gat3 reduction in the thalamus increases seizure risk, and Gat3 increase in the striatum contribute to repetitive behaviors.
” Because our study is the first to look at Gat3 effects on a population level, it might help tie that back to some of the behavioral phenotypes people have been seeing”, Park said.
Sur noted that there are other Gat proteins, such as Gat1, that the brain might use to make up for, so more research is required.
The paper’s other authors are Grayson Sipe, Xin Tang, Prachi Ojha, Giselle Fernandes, Yi Ning Leow, Caroline Zhang, Yuma Osako, Arundhati Natesan, Gabrielle Drummond, and Rudolf Jaenisch.
Funding: The National Institutes of Health, a MURI Grant, The Simons Foundation Autism Research Initiative, the Freedom Together Foundation and The Picower Institute for Learning and Memory provided funding for the study.
About this news about neurotransmission and astrocytes research
Author: David Orenstein
Source: Picower Institute at MIT
Contact: David Orenstein – Picower Institute at MIT
Image: The image is credited to Neuroscience News
Original Research: Open access.
Mriganka Sur and colleagues ‘” Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing.” eLife
Abstract
Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing
Express GABA transporter 3 ( Gat3 ), an astrocyte-specific GABA transporter responsible for maintaining extra-synaptic GABA levels, is increasingly recognized as one of the most important components of brain circuits that regulate a range of functions.
We’ve examined Gat3’s functional role in astrocyte-mediated neuronal activity and information encoding.
First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice.
We observed changes in spontaneous and visually-driven single neuronal response properties, such as response magnitudes and trial-to-trial variability, using in vivo and two-photon calcium imaging of visual cortex neurons in Gat3 knockout mice.
Gat3 knockout had a significant impact on population-level neuronal activity, altering neuronal populations ‘ response dynamics and limiting their ability to accurately represent stimulus information.
These findings demonstrate that Gat3 in astrocytes profoundly shapes the sensory information encoding capacity of neurons and networks within the visual cortex.
