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PKA 驱动海马体 LTP 期间 AMPA 受体单通道电导的增加。

PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus.

机构信息

Glutamate Receptor Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.

Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Korea.

出版信息

Nat Commun. 2021 Jan 18;12(1):413. doi: 10.1038/s41467-020-20523-3.

DOI:10.1038/s41467-020-20523-3
PMID:33462202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7814032/
Abstract

Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTP). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTP), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTP whilst PKA is additionally required for LTP. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

摘要

长时程增强（LTP）在海马 CA1 突触可以通过增加 AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体的数量（N）或其单通道电导（γ）来表达。在这里，我们已经确定了这些不同的突触过程如何有助于从小鼠成年海马切片中 LTP 的表达。由压缩 theta 爆发刺激（TBS）诱导的 LTP，间隔 10 秒，仅涉及 N 的增加（LTP）。相比之下，间隔 10 分钟的 TBS 或当 PKA 被激活时给予的单个 TBS，导致 LTP 与 γ 的短暂增加（LTP）相关，这是由钙通透性（CP）-AMPA 受体的插入引起的。CaMKII 的激活对于 LTP 是必要且充分的，而 PKA 对于 LTP 也是必需的。因此，这两种在机制上不同的 LTP 形式在这些突触中共存。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/a6cf55cbbe00/41467_2020_20523_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/1ec29e8851ee/41467_2020_20523_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/971f42cde6ee/41467_2020_20523_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/0d2f1f7fb7aa/41467_2020_20523_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/ae0e563bab94/41467_2020_20523_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/a1bef93cc23c/41467_2020_20523_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/bb72b07cf223/41467_2020_20523_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/8789cd8c6732/41467_2020_20523_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/a6cf55cbbe00/41467_2020_20523_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/1ec29e8851ee/41467_2020_20523_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/971f42cde6ee/41467_2020_20523_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/0d2f1f7fb7aa/41467_2020_20523_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/ae0e563bab94/41467_2020_20523_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/a1bef93cc23c/41467_2020_20523_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/bb72b07cf223/41467_2020_20523_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/8789cd8c6732/41467_2020_20523_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7814032/a6cf55cbbe00/41467_2020_20523_Fig8_HTML.jpg

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