Depotentiation depends on IP3 receptor activation sustained by synaptic inputs after LTP induction
Depotentiation depends on IP3 receptor activation sustained by synaptic inputs after LTP induction
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DOI：
10.1101/lm.050344.119
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发表时间：
2020-02-01
影响因子：
2
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
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作者：
Fujii, Satoshi;Yamazaki, Yoshihiko;Mikoshiba, Katsuhiko
在豚鼠海马片CA1神经元中，通过向CA1突触传递高频刺激（HFS， 100脉冲，100 Hz）可在场兴奋性突触后电位（epsp）或群体峰（ps）中诱导长期增强（LTP），并在HFS（去增强）后30分钟通过传递低频刺激（LFS，1000脉冲，2 Hz）来逆转长期增强（LTP）。当实验突触刺激在高强度刺激后停止19分钟或在低强度刺激后停止20分钟，或在n -甲基- d -天冬氨酸受体（NMDARs）、I组代谢型谷氨酸受体（mGluRs）或肌醇1,4,5 -三磷酸受体（IP(3)Rs）的拮抗剂存在的相同时间内停止刺激时，这种作用被抑制。在HFS后10分钟或LFS后20分钟，在测试突触输入存在的情况下，应用Ca2+/钙调素依赖性蛋白激酶II （CaMKII）抑制剂或钙调神经磷酸酶抑制剂也可以阻断去电位。这些结果表明，在突触后神经元中，LTP诱导后持续的突触活性导致NMDARs和I组mGluRs的共激活，导致IP(3)Rs和CaMKII的激活，从而导致LFS后钙调磷酸酶的激活和CA1突触反应的去增强。
In CA1 neurons of guinea pig hippocampal slices, long-term potentiation (LTP) was induced in field excitatory postsynaptic potentials (EPSPs) or population spikes (PSs) by the delivery of high-frequency stimulation (HFS, 100 pulses at 100 Hz) to CA1 synapses, and was reversed by the delivery of a train of low-frequency stimulation (LFS,1000 pulses at 2 Hz) at 30 min after HFS (depotentiation), and this effect was inhibited when test synaptic stimulation was halted for a 19-min period after HFS or for a 20-min period after LFS or applied over the same time period in the presence of an antagonist of N-methyl-D-aspartate receptors (NMDARs), group I metabotropic glutamate receptors (mGluRs), or inositol 1, 4, 5-trisphosphate receptors (IP(3)Rs). Depotentiation was also blocked by the application of a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor or a calcineurin inhibitor applied in the presence of test synaptic input for a 10-min period after HFS or for a 20-min period after LFS. These results suggest that, in postsynaptic neurons, the coactivation of NMDARs and group I mGluRs due to sustained synaptic activity following LTP induction results in the activation of IP(3)Rs and CaMKII, which leads to the activation of calcineurin after LFS and depotentiation of CA1 synaptic responses.