Unité Mixte de Recherche_S 1072, Aix Marseille Université, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Secteur Nord, Marseille, France 13015.
Unité Mixte de Recherche_S 1072, Aix Marseille Université, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Secteur Nord, Marseille, France 13015
J Neurosci. 2022 Oct 5;42(40):7530-7546. doi: 10.1523/JNEUROSCI.2331-21.2022. Epub 2022 Sep 9.
Action potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. As it greatly varies between neuronal types, AP shape is also used to distinguish neuronal populations. For instance, AP duration ranges from hundreds of microseconds in cerebellar granule cells to 2-3 ms in SNc dopaminergic (DA) neurons. While most of this variation across cell types seems to arise from differences in the voltage- and calcium-gated ion channels expressed, a few studies suggested that dendritic morphology also affects AP shape. AP duration also displays significant variability in a same neuronal type, although the determinants of these variations are poorly known. Using electrophysiological recordings, morphological reconstructions, and realistic Hodgkin-Huxley modeling, we investigated the relationships between dendritic morphology and AP shape in rat SNc DA neurons from both sexes. In this neuronal type where the axon arises from an axon-bearing dendrite (ABD), the duration of the somatic AP could be predicted from a linear combination of the ABD and non-ABDs' complexities. Dendrotomy experiments and simulation showed that these correlations arise from the causal influence of dendritic topology on AP duration, due in particular to a high density of sodium channels in the somatodendritic compartment. Surprisingly, computational modeling suggested that this effect arises from the influence of sodium currents on the decaying phase of the AP. Consistent with previous findings, these results demonstrate that dendritic morphology plays a major role in defining the electrophysiological properties of SNc DA neurons and their cell-to-cell variations. Action potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. AP shape (e.g., duration) greatly varies between neuronal types but also within a same neuronal type. While differences in ion channel expression seem to explain most of AP shape variation across cell types, the determinants of cell-to-cell variations in a same neuronal type are mostly unknown. We used electrophysiological recordings, neuronal reconstruction, and modeling to show that, because of the presence of sodium channels in the somatodendritic compartment, a large part of cell-to-cell variations in somatic AP duration in substantia nigra pars compacta dopaminergic neurons is explained by variations in dendritic topology.
动作电位 (AP) 形态是一个关键的电生理参数，特别是因为它强烈调节神经递质的释放。由于它在神经元类型之间有很大的差异，AP 形态也被用于区分神经元群体。例如，AP 持续时间从小脑颗粒细胞的数百微秒到 SNc 多巴胺能 (DA) 神经元的 2-3 毫秒不等。虽然这种跨细胞类型的变化似乎主要是由于表达的电压和钙门控离子通道的差异引起的，但有一些研究表明树突形态也会影响 AP 形态。尽管这些变化的决定因素知之甚少，但在同一神经元类型中，AP 持续时间也显示出显著的可变性。使用电生理记录、形态重建和现实的 Hodgkin-Huxley 建模，我们研究了两性大鼠 SNc DA 神经元的树突形态和 AP 形态之间的关系。在这种神经元类型中，轴突起源于带有轴突的树突 (ABD)，体部 AP 的持续时间可以通过 ABD 和非 ABD 的复杂度的线性组合来预测。树突切除术实验和模拟表明，这些相关性是由于树突拓扑结构对 AP 持续时间的因果影响引起的，这主要是由于钠通道在体树突区的高密度。令人惊讶的是，计算模型表明，这种效应是由于钠电流对 AP 衰减相的影响引起的。与以前的发现一致，这些结果表明，树突形态在定义 SNc DA 神经元的电生理特性及其细胞间变化方面起着重要作用。动作电位 (AP) 形态是一个关键的电生理参数，特别是因为它强烈调节神经递质的释放。AP 形态（例如，持续时间）在神经元类型之间有很大的差异，但在同一神经元类型内也有很大的差异。虽然离子通道表达的差异似乎解释了跨细胞类型的 AP 形态变化的大部分，但同一神经元类型内的细胞间变化的决定因素大多未知。我们使用电生理记录、神经元重建和建模来表明，由于钠通道存在于体树突区，黑质致密部多巴胺能神经元体部 AP 持续时间的细胞间变化的很大一部分是由树突拓扑的变化来解释的。
