Department of Physiology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
J Physiol. 2018 Sep;596(17):4141-4156. doi: 10.1113/JP275999. Epub 2018 Jun 28.
High-frequency stimulation (HFS) of the Schaffer collateral pathway activates metabotropic glutamate receptor 5 (mGluR5) signalling in the proximal apical dendrites of CA1 pyramidal neurons. The synaptic activation of mGluR5-mediated calcium signalling causes a significant increase in persistent sodium current (I ) in the dendrites. Increased I by HFS underlies potentiation of synaptic inputs at both the proximal and distal dendrite, leading to an enhanced probability of action potential firing associated with decreased action potential thresholds. Therefore, HFS-induced activation of intracellular mGluR5 serves an important role as an instructive signal for potentiation of upcoming inputs by increasing dendritic excitability.
Dendritic Na channels in pyramidal neurons are known to amplify synaptic signals, thereby facilitating action potential (AP) generation. However, the mechanisms that modulate dendritic Na channels have remained largely uncharacterized. Here, we report a new form of short-term plasticity in which proximal excitatory synaptic inputs to hippocampal CA1 pyramidal neurons transiently elevate dendritic excitability. High-frequency stimulations (HFS) to the Schaffer collateral (SC) pathway activate mGluR5-dependent Ca signalling in the apical dendrites, which, with calmodulin, upregulates specifically Nav1.6 channel-mediated persistent Na currents (I ) in the dendrites. This HFS-induced increase in dendritic I results in transient increases in the amplitude of excitatory postsynaptic potentials induced by both proximal SC and distal perforant path stimulation, leading to the enhanced probability of AP firing associated with decreased AP thresholds. Taken together, our study identifies dendritic I as a novel target for mediating activity-dependent modulation of dendritic integration and neuronal output.
高频刺激（HFS）沙费尔侧支通路激活代谢型谷氨酸受体 5（mGluR5）在 CA1 锥体神经元的近端顶树突中的信号转导。mGluR5 介导的钙信号的突触激活导致树突中持续钠电流（I）的显著增加。HFS 引起的 I 增加是近端和远端树突中突触输入增强的基础，导致与动作电位阈值降低相关的动作电位发射的可能性增加。因此，HFS 诱导的细胞内 mGluR5 的激活作为一种指导信号，通过增加树突兴奋性，增强即将到来的输入的增强。
已知树突中的锥体神经元 Na 通道放大突触信号，从而促进动作电位（AP）的产生。然而，调节树突 Na 通道的机制在很大程度上仍未得到描述。在这里，我们报告了一种新的短期可塑性形式，其中海马 CA1 锥体神经元的近端兴奋性突触输入短暂地增加树突兴奋性。沙费尔侧支（SC）通路的高频刺激（HFS）激活了顶树突中的 mGluR5 依赖性 Ca 信号转导，钙调蛋白特异性地上调 Nav1.6 通道介导的树突Persistent Na 电流（I）。这种 HFS 诱导的树突 I 的增加导致由近端 SC 和远端穿通路径刺激诱导的兴奋性突触后电位的幅度短暂增加，导致与动作电位阈值降低相关的动作电位发射的可能性增加。总之，我们的研究确定了树突 I 作为介导活动依赖性调节树突整合和神经元输出的新型靶标。
