Science: A textbook discovery! Astrocytes regulate neural circuits through electrical activity

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Astrocytes in the gray matter can control the number of synapses, clear the neurotransmitters released by synapses, regulate blood flow, and provide lactic acid for neurons
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But the role of these astrocytes in white matter is not very clear
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Neural circuit function can be regulated by changes in axonal conduction velocity
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Functional changes in the initial segment of axons and Langfei’s junction can cause axon conduction velocity.
Oligodendrocytes can reduce axon capacitance by wrapping the axon of a neuron with myelin, thereby providing high conduction velocity for action potentials
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On October 15, 2021, the David Attwell research team of University College London Neuroscience published an article in Science Zhang, revealing that astrocytes affect neuronal function by regulating the excitability and electrical conduction velocity of axons
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Astrocytes are in close contact with axons and internodal sheaths.
Immunofluorescence experiments have found that astrocytes have close contact with key structures (myelinated axons, internodal sheaths) that control the conduction speed of action potentials.
This structural connection may be a "bridge" for astrocytes to regulate neuronal functions
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In vitro cell experiments found that the branch calcium signal of astrocytes close to the dendrites was significantly increased when the cortical vertebral neurons fired rapidly, but the branch calcium signal of astrocytes close to the axon was not There is no obvious change
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However, there is no such difference in the calcium ion changes of astrocytes in the process of delayed neuron firing
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Previous studies have shown that astrocytes regulate neuronal functions by releasing ATP
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Researchers also found that the release of ATP from astrocytes increased after electrical stimulation of neurons
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After ATP is released, it is quickly hydrolyzed by adenosine triphosphatase on astrocytes and microglia
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Subsequent experiments found that A2a adenosine receptors were abundantly expressed in the initial segment of axons and Langfei's junctions of myelinated axons of neurons, but A2b and A1 adenosine receptors were not expressed
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The A2a adenosine receptor can promote intracellular cyclic AMP levels, and hyperpolarization activates the opening of cyclic nucleotide gated (HCN) channels to regulate cell excitability
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Immunofluorescence revealed that HCN was enriched and expressed in the initial segment of axons and Langfei’s junction
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The expression of A2a adenosine receptor and HCN at the initial segment of axons and Langfei’s junction provides a rich material basis for astrocytes to regulate the electrical activities of neurons
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The activation of A2a adenosine receptors can quickly lead to neuronal hyperpolarization.
This hyperpolarization will cause a time-dependent increase in inward current.
After inhibiting the HCN pathway, the effect of increasing inward current is cancelled
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Calcium uncaging technique transiently increases the calcium ion of astrocytes.
Researchers use calcium uncaging technique to transiently increase the calcium ion concentration of astrocytes and then reduce the axon conduction velocity.
This is the same as incubating A2a adenosine at the node.
The effect of receptor agonists is the same
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Suppressing the HCN channel can hinder the aforementioned reduction in conduction velocity
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A diagram of the mechanism of astrocytes regulating the electrical activity of neurons.
In summary, this article reveals that astrocytes can regulate the excitability of neurons by increasing the concentration of adenosine near the axon initiation segment or the node of Langfei’s node.
It can also regulate the conduction velocity of myelinated axons and regulate the function of neural circuits in a brand-new way
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[References] https://doi.
org/10.
1126/science.
abh2858 The pictures in the text are from the references