Dynamic of axonal activity during fast network oscillations and plasticity

在海马锥体细胞中，与其他神经元一样，动作电位的起始发生在靠近体细胞的轴突。ap也可以在远离体细胞的区域产生，在轴突的异位位置，作为神经元网络的一种涌现的固有特性。我们将研究在正常的生理网络活动（如伽马频率振荡）期间，这种异位生成的ap （eap）可能在海马主要细胞的突触前轴突末端启动的可能性。含有小白蛋白的体周靶向轴突-轴突细胞（AACs）在锥体细胞的策略位点，即轴突初始段（AIS）形成突触。我们将研究这种细胞类型是否可能在伽马振荡期间常规地将eap的繁殖限制在体细胞内，因此可能对主细胞的兴奋性产生关键影响。配对记录将显示突触前AACs的激活是否导致EAPs对单突触偶联主细胞亲本体细胞的侵袭受到抑制。我们将进一步研究AP反向传播的抑制是否通过膜电位超极化/去极化或分流抑制介导。我们假设AACs对锥体细胞轴突突反向传播的调节/抑制允许轴突独立于它们的躯体发射并将它们的信息传递给突触后目标，同时在相关的生理网络活动中省去了复杂的树突整合。

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.