Science's new discovery: the "transmission" of nerve impulses in white matter, astrocytes can regulate the excitability and conduction velocity of myelinated axons

Written | Edited by Qi | Enzyme Astrocytes support the neuronal function of the entire central nervous system
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In gray matter, they regulate the number of synapses during development, remove neurotransmitters released by synapses to stop their effects and prevent excitotoxicity, regulate blood flow to ensure adequate energy supply, and release ATP and other effects on nerves.
Meta-receptors respond to the increase of intracellular calcium concentration ([Ca2+]) with the glial transmitter that regulates information processing [1]
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However, their role in white matter is unclear
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Not long ago, the David Attwell team from UCL published an article in Science magazine entitled "Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed".
This work found that the neuronal activity of rodents can cause The calcium ion concentration in astrocytes near the axon initial segment (AIS) and the site where the action potential is generated in the Langfei node triggers the release of ATP, which is converted into adenosine outside the cell and passes through the A2a receptor (A2aRs) activate the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, which mediates the internal hyperpolarization activation current (Ih) to depolarize the cell, thereby regulating AIS The excitability and action potential conduction velocity affect the function of myelinated axons in the white matter
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The team first used glial fibrillary acidic protein (GFAP) to label astrocytes in the entire gray matter and white matter regions
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It was observed by patch clamp that astrocytes are closely related to the myelinated axons and internode sheaths of the pyramidal cells of the V-th cortex.
When the pyramidal cells are briefly stimulated, the calcium ion concentration in the astrocytes is obvious Rise
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It has been previously reported that in gray matter, astrocytes can regulate neuronal function by releasing ATP, and extracellular ATPase can rapidly hydrolyze ATP into adenosine [2, 3].
The team also tested in white matter At the same time, immunohistochemistry also showed that A2a adenosine receptors exist in 92% of AIS and 85% of Langfei nodes, and AIS expressing these receptors Leading to the corpus callosum, suggesting that these neurons are excitatory neurons
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A2aRs can increase the level of cyclic AMP and affect the excitability of neurons by promoting the opening of the HCN channels present in axons [4].
The team detected HCN2 channel subtypes in 51% of AIS and 64% of Langfei nodes.

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In order to further understand the functionality of these A2aRs and HCN2 channels found at the AIS and Langfei nodes, the team continued to perform patch-clamp recording of the V-th vertebral neurons, combined with the MATLAB model of myelinated axons [5]
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During this period, using the A2aRs agonist CGS 21680 or the Ih blocker ZD7288 to treat different positions of the cell, it can be found that the activation of A2aRs at the node will cause a significant decrease in the conduction velocity, and the Ih block can prevent the velocity from decreasing
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Previous studies have suggested that the regulation of synaptic function by astrocytes in gray matter is the main determinant of neuronal function.
This study reveals a new function of astrocytes involved in the regulation of neural circuits, that is, the regulation of excitatory nerves.
The excitability of meta-AIS and the conduction velocity of myelinated axons
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Therefore, when adenosine levels increase during prolonged waking periods or in response to complex motor behaviors and pathological conditions, the decrease in the conduction velocity of myelinated axons caused by adenosine may change information processing and cognition
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Combining previously reported behavioral effects related to exploratory activity, aggressiveness and anxiety, as well as pathological effects such as epilepsy, Parkinson’s disease, Alzheimer’s disease, and depression, are all related to impaired adenosine signaling.
The discovery is of great significance for the research of this type of disease
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Original link: https://doi.
org/10.
1126/science.
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