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Long-term potentiation (LTP) is the most classic synaptic plasticity of the hippocampus
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From the perspective of time, LTP can be divided into early LTP (caused by a single high-frequency stimulation) and late LTP (induced by multiple high-frequency stimulation) dependent on protein synthesis
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Calcium ion signals in the fine structure dendrites and axon branches of neurons usually respond within a few milliseconds, while the calcium ion transients in astrocytes can last for several seconds to several minutes.
Information is connected to achieve a higher level of information integration
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The calcium event of astrocytes mainly depends on the inositol triphosphate (IP3) type 2 receptor (IP3R2), which regulates LTP
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On October 12, 2021, Professor Gao Tianming, School of Basic Medical Sciences, Southern Medical University, published an article revealing the difference between astrocytes and neurons in regulating synaptic plasticity, and this difference is also reflected in different stages of memory
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Researchers found that IP3R2 knockout mouse hippocampal CA1 brain slices can normally induce early LTP after receiving a single high-frequency stimulation, but cannot induce late-stage LTP after receiving 4 high-frequency stimulation
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The specific knockout of IP3R2 on astrocytes has no effect on early LTP, but there are obstacles in inducing late LTP
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In addition, knocking out IP3R2 caused the hippocampus this kind of synaptic plasticity disorder, but did not cause changes in the morphology of astrocytes and the number of synapses in neurons
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Further chemical genetics technology can specifically enhance the cell body and branch calcium ion signal of normal mouse astrocytes, but it will not cause changes in the calcium ion signal of the cell body of IP3R2 knockout mouse astrocytes
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In addition, two-photon microscopy imaging technology found that repeated high-frequency stimulation can cause a progressive increase in the soma and branch calcium signal of normal mouse astrocytes, but this calcium ion does not exist in IP3R2 knockout mice.
The integration of signals indicates that knocking out IP3R2 causes the integration of calcium ion signals in astrocytes, so the calcium ion signals cannot be enhanced
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Astrocytes release glutamate, brain-derived neurotrophic factor (BDNF), D-serine and ATP, among which BDNF can induce the formation of late LTP and promote the formation and storage of long-term memory
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The level of BDNF in the hippocampus of the IP3R2 knockout mice and the specific knockout IP3R2 mice of astrocytes decreased significantly, indicating that the formation of BDNF was reduced after inhibiting the activity of astrocytes
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The researchers used a variety of tools in mice to specifically knock out BDNF on astrocytes and inhibit the formation of late LTP.
However, the expression of BDNF through a viral strategy can reverse this synaptic plasticity disorder, which indicates that astrology Glial cell BDNF is necessary for the induction of late LTP
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Subsequent experiments confirmed that neuron-derived BDNF is critical for the formation of early and late LTP
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LTP in the hippocampus is critical for the formation of memory
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Researchers used the conditional fear memory model and found that after knocking out IP3 or knocking out BDNF in astrocytes, there are obstacles to the formation of long-term memory after fear training.
This obstacle disappears after re-expression of BDNF
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After knocking out the neuron-derived BDNF, the memory cannot be formed correctly during the training phase.
There are obstacles to the formation of subsequent short-term and long-term memory, which indicates that different forms of LTP affect different stages of memory, and this difference Related to the source of BDNF
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In general, this paper found that the IP3R2-dependent calcium ion signal of astrocytes is necessary for the formation of late LTP.
It was further found that BDNF derived from neurons and BDNF derived from astrocytes can form LTP at different stages, and The controlled memory behavior is also different
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[References] https://doi.
org/10.
1038/s41380-021-01332-6 The pictures in the article are from the references