Petersen Anders V, Jensen Camilla S, Crépel Valérie, Falkerslev Mathias, Perrier Jean-François
Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.
Department of Biomedical Sciences, University of Copenhagen Copenhagen, Denmark.
Front Cell Neurosci. 2017 Mar 7;11:60. doi: 10.3389/fncel.2017.00060. eCollection 2017.
The subiculum is the main output of the hippocampal formation. A high proportion of its principal neurons fire action potentials in bursts triggered by the activation of low threshold calcium currents. This firing pattern promotes synaptic release and regulates spike-timing-dependent plasticity. The subiculum receives a high density of fibers originating from the raphe nuclei, suggesting that serotonin (5-HT) modulates subicular neurons. Here we investigated if and how 5-HT modulates the firing pattern of bursting neurons. By combining electrophysiological analysis with pharmacology, optogenetics and calcium imaging, we demonstrate that 5-HT receptors reduce bursting activity by inhibiting a low-threshold calcium current mediated by T-type Ca channels in principal cells of the subiculum. In addition, we show that the activation of this novel pathway decreases bursting activity and the occurrence of epileptiform discharges induced in models for temporal lobe epilepsy (TLE).
海马下脚是海马结构的主要输出部位。其大部分主要神经元在低阈值钙电流激活引发的爆发中产生动作电位。这种放电模式促进突触释放并调节依赖于动作电位时间的可塑性。海马下脚接受来自中缝核的高密度纤维投射，提示血清素（5-羟色胺，5-HT）可调节海马下脚神经元。在此，我们研究了5-HT是否以及如何调节爆发性神经元的放电模式。通过将电生理分析与药理学、光遗传学和钙成像相结合，我们证明5-HT受体通过抑制海马下脚主要细胞中由T型钙通道介导的低阈值钙电流来降低爆发活动。此外，我们还表明，激活这一新通路可降低爆发活动以及在颞叶癫痫（TLE）模型中诱发的癫痫样放电的发生率。
