Dynamic of axonal activity during fast network oscillations and plasticity

与其他神经元一样，在海马锥体细胞中，动作电位(AP)的起始发生在靠近胞体的轴突。AP也可以在远离胞体的区域，在轴突的异位位置产生，作为神经元网络的一种新的固有特性。我们将研究这种异位产生的AP(EAP)可能是在正常的生理网络活动中(如伽马频率振荡)在海马主细胞的突触前轴突终末启动的。含有小白蛋白的周边靶向轴突细胞(AAC)在锥体细胞的关键部位形成突触，即在轴突起始段(AIS)。我们将研究这种细胞类型在伽马振荡期间常规地限制EAP到胞体的传播的可能性，从而可能对主细胞的兴奋性产生关键影响。配对的记录将显示，突触前AAC的激活是否导致抑制EAP对单突触耦合主细胞亲本胞体的侵袭。我们将进一步研究AP反向传播的抑制是通过膜电位超极化/去极化还是分流抑制来实现的。我们假设，AAC对沿锥体细胞轴突的棘波反向传播的调制/抑制允许轴突独立于其胞体发出信号，并将其信息传递到突触后靶点，同时在相关的生理网络活动中避免复杂的树突整合。

In hippocampal pyramidal cells, as in other neurons, initiation of action potentials (APs) occurs in the axon close to the soma. APs can also be generated at regions remote from the soma, at ectopic sites of the axon, as an emergent intrinsic property of the neuronal network. We will examine the possibility that such ectopically generated APs (EAPs) may be initiated at presynaptic axon terminals of principal cells of the hippocampus during normal physiological network activity such as gamma frequency oscillations. Parvalbumin containing perisomatic targeting axo-axonic cells (AACs) form synapses at strategic sites of pyramidal cells, namely at the axon initial segment (AIS). We will investigate the possibility that this cell type could routinely confine the propagation of EAPs to the soma during the gamma oscillations and therefore may have critical impact on the excitability of principal cells. Paired recordings will show whether activation of presynaptic AACs results in suppression of EAPs invasion to the parent soma of monosynaptically coupled principal cells. We will further examine whether suppression of AP back-propagation is mediated through a membrane potential hyperpolarization/ depolarization or a shunting inhibition. We hypothesise that the modulation/suppression of spike backpropagation along the pyramidal cell axon by AACs allows axons to fire independently from their somata and to transmit their message to the postsynaptic targets, whilst at the same time to spare the complex dendritic integration during relevant physiological network activity.