Postganglionic sympathetic neurons, but not locus coeruleus optostimulation, activates neuromuscular transmission in the adult mouse in vivo

• Published in: Molecular and cellular neuroscience Vol. 109; p. 103563
• Main Authors: Wang, Zhong-Min, Messi, Maria L., Grinevich, Valentina, Budygin, Evgeny, Delbono, Osvaldo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2020
• Subjects: Neuromuscular junction; Neuromuscular transmission; Skeletal muscle; Sympathetic nervous system; Sympathetic nervous system; Neuromuscular transmission; Neuromuscular junction; Skeletal muscle
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2020.103563

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.
•We investigated the role of peripheral and central sympathetic relays on NMJ transmission in living adult mice•Selective optoactivation of postganglionic sympathetic neurons increases NMJ transmission in vitro and in vivo•β1-adrenergic receptors mediate the influence of catecholamines on motoneuron synaptic vesicle release•LC neurons projecting to preganglionic sympathetic neurons (IML) do not regulate NMJ transmission.