Meiser Sonja, Sleeboom Jana Marie, Arkhypchuk Ihor, Sandbote Kevin, Kretzberg Jutta
Department of Neuroscience, Computational Neuroscience, Faculty VI, University of Oldenburg, Oldenburg, Germany.
Institute of Physiology II, Faculty of Medicine, University Clinic Bonn (UKB), University of Bonn, Bonn, Germany.
Front Cell Neurosci. 2023 Jul 25;17:1186997. doi: 10.3389/fncel.2023.1186997. eCollection 2023.
Mechanosensory cells in the leech share several common features with mechanoreceptors in the human glabrous skin. Previous studies showed that the six T (touch) cells in each body segment of the leech are highly variable in their responses to somatic current injection and change their excitability over time. Here, we investigate three potential reasons for this variability in excitability by comparing the responses of T cells at two soma locations (T2 and T3): (1) Differential effects of time-dependent changes in excitability, (2) divergent synaptic input from the network, and (3) different anatomical structures. These hypotheses were explored with a combination of electrophysiological double recordings, 3D reconstruction of neurobiotin-filled cells, and compartmental model simulations. Current injection triggered significantly more spikes with shorter latency and larger amplitudes in cells at soma location T2 than at T3. During longer recordings, cells at both locations increased their excitability over time in the same way. T2 and T3 cells received the same amount of synaptic input from the unstimulated network, and the polysynaptic connections between both T cells were mutually symmetric. However, we found a striking anatomical difference: While in our data set all T2 cells innervated two roots connecting the ganglion with the skin, 50% of the T3 cells had only one root process. The sub-sample of T3 cells with one root process was significantly less excitable than the T3 cells with two root processes and the T2 cells. To test if the additional root process causes higher excitability, we simulated the responses of 3D reconstructed cells of both anatomies with detailed multi-compartment models. The anatomical subtypes do not differ in excitability when identical biophysical parameters and a homogeneous channel distribution are assumed. Hence, all three hypotheses may contribute to the highly variable T cell responses, but none of them is the only factor accounting for the observed systematic difference in excitability between cells at T2 vs. T3 soma location. Therefore, future patch clamp and modeling studies are needed to analyze how biophysical properties and spatial distribution of ion channels on the cell surface contribute to the variability and systematic differences of electrophysiological phenotypes.
水蛭中的机械感觉细胞与人类无毛皮肤中的机械感受器具有一些共同特征。先前的研究表明,水蛭每个体节中的六个T(触觉)细胞对体细胞电流注入的反应高度可变,并且其兴奋性会随时间变化。在这里,我们通过比较T细胞在两个胞体位置(T2和T3)的反应,研究兴奋性这种变异性的三个潜在原因:(1)兴奋性随时间变化的差异效应,(2)来自网络的不同突触输入,以及(3)不同的解剖结构。我们结合电生理双记录、神经生物素填充细胞的三维重建和房室模型模拟来探讨这些假设。电流注入在胞体位置T2的细胞中引发的动作电位明显更多,潜伏期更短,幅度更大,而在T3处则不然。在更长时间的记录中,两个位置的细胞兴奋性都以相同的方式随时间增加。T2和T3细胞从未受刺激的网络接收相同数量的突触输入,并且两个T细胞之间的多突触连接是相互对称的。然而,我们发现了一个显著的解剖学差异:在我们的数据集中,所有T2细胞都支配着两条连接神经节与皮肤的神经根,而50%的T3细胞只有一个根突。具有一个根突的T3细胞子样本的兴奋性明显低于具有两个根突的T3细胞和T2细胞。为了测试额外的根突是否会导致更高的兴奋性,我们用详细的多房室模型模拟了两种解剖结构的三维重建细胞的反应。当假设相同的生物物理参数和均匀的通道分布时,解剖学亚型在兴奋性上没有差异。因此,所有这三个假设可能都导致了T细胞反应的高度变异性,但它们都不是解释T2和T3胞体位置细胞之间观察到的兴奋性系统差异的唯一因素。因此,未来需要进行膜片钳和建模研究,以分析细胞表面离子通道的生物物理特性和空间分布如何导致电生理表型的变异性和系统差异。