一种新颖的轴突断端(axon bleb)膜片钳记录方法大力促进了中枢神经系统轴突功能的研究。我们的工作应用这一方法揭示了大脑皮层锥体神经元的数码信号(具全或无特性的动作电位)的爆发和传播机制。在轴突始段(axon initial segment,AIS)远端高密度聚集的低阈值Na+通道亚型Nav1.6决定动作电位的爆发;而在AIS近端高密度聚集的高阈值Na+通道亚型Nav1.2促进动作电位向胞体和树突的反向传播。应用胞体和轴突的同时记录,我们发现胞体阈下膜电位的变化可以在轴突上传播较长的距离并可到达那些离胞体较近的突触前终末。进一步的研究证明了胞体膜电位的变化调控动作电位触发的突触传递,该膜电位依赖的突触传递是一种模拟式的信号传递。轴突上一类特殊K+通道(Kv1)的活动调制动作电位的波形,特别是其波宽,从而调控各种突触前膜电位水平下突触强度的变化。突触前终末的背景Ca^2+浓度也可能参与模拟信号的传递。这些发现深化了我们对中枢神经系统内神经信号处理基本原理的认识,进而帮助我们理解脑如何工作。
A new method of axon recording through axon bleb has boosted the studies on the functional role of central nervous system(CNS) axons.Using this method,we have revealed the mechanisms underlying the initiation and propagation of the digital-mode signal,all-or-none action potentials(APs),in neocortical pyramidal neurons.Accumulation of the low-threshold Na+ channel subtype Nav1.6 at the distal end of the axon initial segment(AIS) determines the lowest threshold for AP initiation,whereas accumulation of the high-threshold subtype Nav1.2 at the proximal region of the AIS promotes AP backpropagation to the soma and dendrites.Through dual recording from the soma and the axon,we have showed that subthreshold membrane potential(Vm) fluctuations in the soma propagate along the axon to a long distance and probably reach the axon terminals.Paired recording from cortical neurons has revealed that these Vm changes in the soma modulate AP-triggered synaptic transmission.This new Vm-dependent mode of synaptic transmission is called analog communication.Unique properties of axonal K+ channels(Kv1 channels) may contribute to shaping the AP waveform,particularly its duration,and thus controlling synaptic strength at different levels of presynaptic Vm.The level of background Ca^2+ may also participate in mediating the analog signaling.Together,these findings enrich our knowledge on the principles of neuronal signaling in the CNS and help understand how the brain works.