Action potential shape is a major determinant of synaptic transmission, and mechanisms of spike tuning are therefore of key functional significance. We demonstrate that synaptic activity itself modulates future spikes in the same neuron via a rapid feedback pathway. Using Ca²⁺ imaging and targeted uncaging approaches in layer 5 neocortical pyramidal neurons, we show that the single spike-evoked Ca²⁺ rise occurring in one proximal bouton or first node of Ranvier drives a significant sharpening of subsequent action potentials recorded at the soma. This form of intrinsic modulation, mediated by the activation of large-conductance Ca²⁺/voltage-dependent K⁺ channels (BK channels), acts to maintain high-frequency firing and limit runaway spike broadening during repetitive firing, preventing an otherwise significant escalation of synaptic transmission. Our findings identify a novel short-term presynaptic plasticity mechanism that uses the activity history of a bouton or adjacent axonal site to dynamically tune ongoing signaling properties.

中文翻译：

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BK 通道介导的反馈通路将单突触活动与重复放电中的动作电位锐化联系起来。


动作电位形状是突触传递的主要决定因素，因此尖峰调节机制具有关键的功能意义。我们证明突触活动本身通过快速反馈途径调节同一神经元的未来尖峰。使用 Ca ²⁺成像和第 5 层新皮质锥体神经元中的靶向解笼方法，我们表明，在 Ranvier 的一个近端 bouton 或第一个节点中发生的单个尖峰诱发的 Ca ²⁺上升驱动了在体细胞记录的后续动作电位的显着锐化。这种形式的内在调制由大电导 Ca ²⁺ /电压依赖性 K ⁺通道（BK 通道）的激活介导，可维持高频发射并限制重复发射期间的失控尖峰展宽，从而防止其他情况下的显着升级的突触传递。我们的研究结果确定了一种新颖的短期突触前可塑性机制，该机制利用布顿或相邻轴突位点的活动历史来动态调整正在进行的信号传导特性。