Neurons have long attracted attention in the busy circuits of the brain – but a new study shows that non-neuron cells called astrocytes are crucial to keep the performance running.
Astrocytes in the mouse visual cortex can help the neurons process visual information together by regulating the balance of neurotransmitters called GABA, according to new research from the Picower Institute of Learning and Memory at MIT.
Astrocytes fine-tune nerve harmony through GABA transport
The researchers used a specially designed CRISPR/CAS9 system to phase out a protein called GABA Transporter 3 (GAT3) in astrocytes in the visual cortex. GAT3 often helps astrocytes delay additional GABA, a neurotransmitter that inhibits neuronal activity. Without it, neurons are bathed in too much GABA. Although each neuron still responds to visual stimuli, their collective coordination (basically for complex images for processing complex images).
“Even if the changes in individual neurons representing visual stimulation do not change significantly, this may make population levels measurable, measurable significant changes,” senior author Mriganka Sur noted.
How the research is done
Graduate student Jiho Park uses a novel multiplexed CRISPR method called MRCUTS to knock out GAT3 in the visual cortex. The mice then used two-photon calcium imaging to monitor neuronal activity, while the mice watched the visual stimulus. Surprisingly, although individual neurons adjust it to visual features such as line orientation, overall responsiveness and reliability are reduced.
What happened, nothing
- Neurons emit less and have lower frequency
- Keep the direction adjustment complete
- Paired neurons still communicate directly
- Neuron groups become less synchronized
- Cross-population coding information is seriously impaired
Subtle noise, great influence
Using statistical models, the researchers found that when Gat3 is lost, the activity of a neuron becomes less predictable to its neighbors. It is usually improved by machine learning decoders that sample GAT3-deficient brains. This shows that while individual neurons work, their “chorus” are disconnected.
Beyond the visual cortex
These findings may help explain clinical observations in other brain regions of GAT3 dysregulation. For example, too little GAT3 in the thalamus increases the risk of seizures, while too much in the striatum is associated with repetitive behavior. As Parker said, “Our research may help connect it to some of the behavioral phenotypes people see.”
Tools for future research
The MRCUTS system allows researchers to use only a single virus to provide multiple gene editing, an effective method of future astrocyte-specific manipulation in adult animals without developmental confusion.
By diverting attention to astrocytes and their subtle regulatory effects, this study adds new depth to our understanding of how the brain understands the world, rather than the neurons of neurons, but a tightly coordinated ensemble.
Magazine: Elife
doi: 10.7554/Elife.107298.1
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