Ge Renkai, Dai Yue
Shanghai Key Laboratory of Multidimensional Information Processing, School of Communication and Electronic Engineering, East China Normal University, Shanghai, China.
School of Physical Education and Health Care, East China Jiaotong University, Nanchang, China.
Front Cell Neurosci. 2020 Oct 16;14:575626. doi: 10.3389/fncel.2020.575626. eCollection 2020.
Exercise plays a key role in preventing or treating mental or motor disorders caused by dysfunction of the serotonergic system. However, the electrophysiological and ionic channel mechanisms underlying these effects remain unclear. In this study, we investigated the effects of 3-week treadmill exercise on the electrophysiological and channel properties of dorsal raphe nucleus (DRN). Serotonin (5-HT) neurons in ePet-EYFP mice, using whole-cell patch clamp recording. Treadmill exercise was induced in ePet-EYFP mice of P21-24 for 3 weeks, and whole-cell patch clamp recording was performed on EYFP-positive 5-HT neurons from DRN slices of P42-45 mice. Experiment data showed that 5-HT neurons in the DRN were a heterogeneous population with multiple firing patterns (single firing, phasic firing, and tonic firing). Persistent inward currents (PICs) with multiple patterns were expressed in 5-HT neurons and composed of Cav1.3 (Ca-PIC) and sodium (Na-PIC) components. Exercise hyperpolarized the voltage threshold for action potential (AP) by 3.1 ± 1.0 mV (control: = 14, exercise: = 18, = 0.005) and increased the AP amplitude by 6.7 ± 3.0 mV ( = 0.031) and firing frequency by more than 22% especially within a range of current stimulation stronger than 70 pA. A 3-week treadmill exercise was sufficient to hyperpolarize PIC onset by 2.6 ± 1.3 mV (control: -53.4 ± 4.7 mV, = 28; exercise: -56.0 ± 4.7 mV, = 25, = 0.050) and increase the PIC amplitude by 28% (control: 193.6 ± 81.8 pA; exercise: 248.5 ± 105.4 pA, = 0.038). Furthermore, exercise hyperpolarized Na-PIC onset by 3.8 ± 1.8 mV (control: = 8, exercise: = 9, = 0.049) and increased the Ca-PIC amplitude by 23% ( = 0.013). The exercise-induced enhancement of the PIC amplitude was mainly mediated by Ca-PIC and hyperpolarization of PIC onset by Na-PIC. Moreover, exercise facilitated dendritic plasticity, which was shown as the increased number of branch points by 1.5 ± 0.5 ( = 0.009) and dendritic branches by 2.1 ± 0.6 ( = 20, = 0.001) and length by 732.0 ± 100.1 μm ( < 0.001) especially within the range of 50-200 μm from the soma. Functional analysis suggested that treadmill exercise enhanced Na-PIC for facilitation of spike initiation and Ca-PIC for regulation of repetitive firing. We concluded that PICs broadly existed in DRN 5-HT neurons and could influence serotonergic neurotransmission in juvenile mice and that 3-week treadmill exercise induced synaptic adaptations, enhanced PICs, and thus upregulated the excitability of the 5-HT neurons.
运动在预防或治疗由血清素能系统功能障碍引起的精神或运动障碍中起着关键作用。然而，这些作用背后的电生理和离子通道机制仍不清楚。在本研究中，我们研究了为期3周的跑步机运动对背侧中缝核（DRN）电生理和通道特性的影响。使用全细胞膜片钳记录技术，对ePet-EYFP小鼠中血清素（5-HT）神经元进行研究。对P21-24的ePet-EYFP小鼠进行为期3周的跑步机运动诱导，然后对P42-45小鼠DRN切片中EYFP阳性的5-HT神经元进行全细胞膜片钳记录。实验数据表明，DRN中的5-HT神经元是具有多种放电模式（单次放电、相位放电和紧张性放电）的异质群体。5-HT神经元中表达了具有多种模式的持续性内向电流（PICs），其由Cav1.3（Ca-PIC）和钠（Na-PIC）成分组成。运动使动作电位（AP）的电压阈值超极化3.1±1.0 mV（对照组：n = 14，运动组：n = 18，P = 0.005），并使AP幅度增加6.7±3.0 mV（P = 0.031），放电频率增加超过22%，特别是在电流刺激强度大于70 pA的范围内。为期3周的跑步机运动足以使PIC起始超极化2.6±1.3 mV（对照组：-53.4±4.7 mV，n = 28；运动组：-56.0±4.7 mV，n = 25，P = 0.050），并使PIC幅度增加28%（对照组：193.6±81.8 pA；运动组：248.5±105.4 pA，P = 0.038）。此外，运动使Na-PIC起始超极化3.8±1.8 mV（对照组：n = 8，运动组：n = 9，P = 0.049），并使Ca-PIC幅度增加23%（P = 0.013）。运动诱导的PIC幅度增强主要由Ca-PIC介导，PIC起始的超极化由Na-PIC介导。此外，运动促进了树突可塑性，表现为分支点数量增加1.5±0.5（P = 0.009），树突分支增加2.1±0.6（n = 20，P = 0.001），长度增加732.0±100.1 μm（P < 0.001），特别是在距胞体50-200 μm范围内。功能分析表明，跑步机运动增强了Na-PIC以促进动作电位起始，增强了Ca-PIC以调节重复放电。我们得出结论，PICs广泛存在于DRN的5-HT神经元中，可影响幼年小鼠的血清素能神经传递，并且为期3周的跑步机运动诱导了突触适应性变化，增强了PICs，从而上调了5-HT神经元的兴奋性。
