Recent work demonstrated that sympathetic neurons innervate the skeletal muscle near the neuromuscular junction (NMJ), and muscle sympathectomy and sympathomimetic agents strongly influence motoneuron synaptic vesicle release ex vivo. Moreover, reports attest that the pontine nucleus locus coeruleus (LC) projects to preganglionic sympathetic neurons and regulates human mobility and skeletal muscle physiology. Thus, we hypothesized that peripheral and central sympathetic neurons projecting directly or indirectly to the skeletal muscle regulate NMJ transmission. The aim of this study was to define the specific neuronal groups in the peripheral and central nervous systems that account for such regulation in adult mice in vivo by using optogenetics and NMJ transmission recordings in 3–5-month-old, male and female ChR2(H134R/EYFP)/TH-Cre mice. After detecting ChR2(H134R)/EYFP fluorescence in the paravertebral ganglia and LC neurons, we tested whether optostimulating the plantar nerve near the lumbricalis muscle or LC neurons effectively modulates motor nerve terminal synaptic vesicle release in living mice. Nerve optostimulation increased motor synaptic vesicle release in vitro and in vivo, while the presynaptic adrenoceptor blockers propranolol (β1/β2) and atenolol (β1) prevented this outcome. The effect is primarily presynaptic since miniature end-plate potential (MEPP) kinetics remained statistically unmodified after stimulation. In contrast, optostimulation of LC neurons did not regulate NMJ transmission. In summary, we conclude that postganglionic sympathetic neurons, but not LC neurons, increased NMJ transmission by acting on presynaptic β1-adrenergic receptors in vivo.

最近的工作表明，交感神经元支配神经肌肉接头 (NMJ) 附近的骨骼肌，肌肉交感神经切除术和拟交感神经药物强烈影响离体运动神经元突触囊泡的释放。此外，报告证明桥脑蓝斑核 (LC) 投射到节前交感神经元并调节人类活动能力和骨骼肌生理机能。因此，我们假设直接或间接投射到骨骼肌的外周和中枢交感神经元调节 NMJ 传递。本研究的目的是通过使用光遗传学和 3-5 个月大的雄性和雌性 ChR2（ H134R/EYFP)/TH-Cre 小鼠。在检测到椎旁神经节和 LC 神经元中的 ChR2(H134R)/EYFP 荧光后，我们测试了光刺激腰肌附近的足底神经或 LC 神经元是否有效调节活小鼠运动神经末梢突触囊泡的释放。神经光刺激增加了体外和体内运动突触小泡的释放，而突触前肾上腺素受体阻滞剂普萘洛尔 (β1/β2) 和阿替洛尔 (β1) 阻止了这一结果。这种影响主要是突触前的，因为微型终板电位 (MEPP) 动力学在刺激后在统计上保持不变。相比之下，LC 神经元的光刺激不调节 NMJ 传输。总之，我们得出结论，节后交感神经元，而不是 LC 神经元，通过在体内作用于突触前 β1-肾上腺素能受体来增加 NMJ 传递。