Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition
Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition
复制标题
DOI：
10.1016/j.cell.2005.07.033
复制
发表时间：
2005-10-07
期刊：
影响因子：
64.5
通讯作者：
Jan, LY
中科院分区：
文献类型：
--
作者：
Huang, CS;Shi, SH;Jan, LY
突触可塑性，与学习和记忆相关的细胞，涉及树突棘中的信号级联。大量研究表明，谷氨酸受体对兴奋性突触后电流（EPSC）的长时程增强（LTP）是由N-甲基-D-谷氨酸受体（NMDA-R）和钙/钙调蛋白依赖性蛋白激酶II（CaMKII）激活引起的。在这里，我们报告，在突触后CA 1锥体神经元中的相同的信号通路也导致慢抑制性突触后电流（sIPSC）的LTP的代谢型GABA（B）受体（GABA（B）-Rs）和G蛋白激活的内向整流钾（GIRK）通道，都驻留在树突棘以及轴介导。兴奋性和抑制性突触可塑性的调节机制的有趣差异的指示，sIPSC而不是EPSC的LTP在缺乏Nova-2的小鼠中被废除，Nova-2是一种神经元特异性RNA结合蛋白，是潜伏性癌症、运动抑制控制减少和痴呆的副肿瘤性眼阵挛肌阵挛共济失调（POMA）患者的自身免疫靶点。
Synaptic plasticity, the cellular correlate for learning and memory, involves signaling cascades in the dendritic spine. Extensive studies have shown that long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) through glutamate receptors is induced by activation of N-methyl-D-asparate receptor (NMDA-R)-the coincidence detector-and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Here we report that the same signaling pathway in the postsynaptic CA1 pyramidal neuron also causes LTP of the slow inhibitory postsynaptic current (sIPSC) mediated by metabotropic GABA(B) receptors (GABA(B)-Rs) and G protein-activated inwardly rectifying K+ (GIRK) channels, both residing in dendritic spines as well as shafts. Indicative of intriguing differences in the regulatory mechanisms for excitatory and inhibitory synaptic plasticity, LTP of sIPSC but not EPSC was abolished in mice lacking Nova-2, a neuronal-specific RNA binding protein that is an autoimmune target in paraneoplastic opsoclonus myoclonus ataxia (POMA) patients with latent cancer, reduced inhibitory control of movements, and dementia.