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: n = 14, exercise: n = 18, p = 0.005) and increased the AP amplitude by 6.7 ± 3.0 mV (p = 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, n = 28; exercise: −56.0 ± 4.7 mV, n = 25, p = 0.050) and increase the PIC amplitude by 28% (control: 193.6 ± 81.8 pA; exercise: 248.5 ± 105.4 pA, p = 0.038). Furthermore, exercise hyperpolarized Na-PIC onset by 3.8 ± 1.8 mV (control: n = 8, exercise: n = 9, p = 0.049) and increased the Ca-PIC amplitude by 23% (p = 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 (p = 0.009) and dendritic branches by 2.1 ± 0.6 (n = 20, p = 0.001) and length by 732.0 ± 100.1 μm (p < 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关键作用。但是，尚不清楚这些作用的电生理和离子通道机制。在这项研究中，我们调查了3周的跑步机运动对背沟核（DRN）的电生理和通道特性的影响。使用全细胞膜片钳记录，在ePet-EYFP小鼠中的血清素（5-HT）神经元。在P21–24的ePet-EYFP小鼠中诱导跑步机运动3周，并对P42–45小鼠DRN切片的EYFP阳性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神经元是异质种群，具有多种放电模式（单次放电，相位放电和补品放电）。具有多个模式的持久性内向电流（PIC）在5-HT神经元中表达，并由Cav1.3（Ca-PIC）和钠（Na-PIC）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：ñ = 14，运动： ñ = 18， p = 0.005）并将AP幅度增加6.7±3.0 mV（p= 0.031），且发射频率超过22％，特别是在电流刺激范围大于70 pA的情况下。为期3周的跑步机锻炼足以使PIC发作超极化2.6±1.3 mV（对照：−53.4±4.7 mV，ñ= 28; 运动：−56.0±4.7 mV，ñ = 25， p = 0.050），并提高PIC幅度28％（对照：193.6±81.8 pA；运动：248.5±105.4 pA， p= 0.038）。此外，以3.8±1.8 mV的运动对超极化Na-PIC发作（对照：ñ = 8，锻炼： ñ = 9 p = 0.049），并将Ca-PIC幅度提高了23％（p= 0.013）。运动引起的PIC振幅增强主要由Ca-PIC介导，而Na-PIC引起PIC发作超极化。此外，运动促进了树突状可塑性，表现为分支点数目增加了1.5±0.5（p = 0.009）和树枝状分支的幅度为2.1±0.6（ñ = 20， p = 0.001）和732.0±100.1μm（p<0.001），尤其是距躯体50-200μm的范围内。功能分析表明，跑步机锻炼可增强Na-PIC来促进尖峰启动，并增强Ca-PIC来调节重复发射。我们得出的结论是，PICS广泛存在于DRN 5-HT神经元中，并且可能影响幼年小鼠的血清素神经传递，并且3周的跑步机运动会引起突触适应，增强PIC，从而上调5-HT神经元的兴奋性。