Schaffer侧支途径的高频刺激(HFS)激活CA1锥体神经元近端顶端树突中的代谢型谷氨酸受体5(mGluR5)信号。mGluR5介导的钙信号的突触激活导致持续钠电流的显着增加(INa,P)在树突中。Ina增加,HFS的P是近端和远端树突上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激发概率增加。因此,HFS诱导的细胞内mGluR5的激活作为通过增加树突兴奋性增强即将到来的输入的指导性信号具有重要作用。
已知锥体神经元中的树突状Na+通道会放大突触信号,从而促进动作电位(AP)的产生。然而,调节树突状Na+通道的机制在很大程度上仍未表征。这里,我们报道了一种新形式的短期可塑性,即海马CA1区锥体神经元的近端兴奋性突触输入可瞬时提高树突的兴奋性.对Schaffer侧支(SC)途径的高频刺激(HFS)激活顶端树突中mGluR5依赖性Ca2信号传导,which,使用钙调蛋白,特别上调Nav1.6通道介导的持续Na+电流(INa,P)在树突中。这种HFS诱导的树突状INa增加,P导致近端SC和远端穿通路径刺激引起的兴奋性突触后电位的振幅瞬时增加。导致与AP阈值降低相关的AP触发概率增加。一起来看,我们的研究确定了树突状INa,P作为介导树突整合和神经元输出的活性依赖性调节的新靶标。
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 (INa,P ) in the dendrites. Increased INa,P 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 Ca2+ signalling in the apical dendrites, which, with calmodulin, upregulates specifically Nav1.6 channel-mediated persistent Na+ currents (INa,P ) in the dendrites. This HFS-induced increase in dendritic INa,P 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 INa,P as a novel target for mediating activity-dependent modulation of dendritic integration and neuronal output.