Homeostatic plasticity induced by increased acetylcholine release at the mouse neuromuscular junction

• Published in: Neurobiology of aging Vol. 110; pp. 13 - 26
• Main Authors: Camargo, WL, Kushmerick, C, Pinto, EKR, Souza, NMV, Cavalcante, WLG, Souza-Neto, FP, Guatimosim, S, Prado, MAM, Guatimosim, C, Naves, LA
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2022
• Subjects: Acetylcholine - metabolism; Age dependent mechanisms; Aging - metabolism; Aging - physiology; Animals; Excitatory Postsynaptic Potentials - physiology; Gene Expression; Homeostasis - physiology; Homeostatic plasticity; Mice; Muscle Contraction - physiology; Neuromuscular junction; Neuromuscular Junction - metabolism; Synaptic Potentials - physiology; Synaptic Transmission - physiology; Vesicular Acetylcholine Transport Proteins - genetics; Vesicular Acetylcholine Transport Proteins - metabolism; Vesicular acetylcholine transporter; Homeostatic plasticity; Age dependent mechanisms; Neuromuscular junction; Vesicular acetylcholine transporter
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2021.10.010

At the neuromuscular junction (NMJ), changes to the size of the postsynaptic potential induce homeostatic compensation. At the Drosophila NMJ, increased glutamate release causes a compensatory decrease in quantal content, but it is unknown if this mechanism operates at the cholinergic mammalian NMJ. We addressed this question by recording endplate potentials (EPP) and muscle contraction in 3-month and 24-month ChAT-ChR2-EYFP mice that overexpress vesicular acetylcholine transporter and release more acetylcholine per vesicle. At 3 months, the quantal content of EPPs from ChAT-ChR2-EYFP mice were not different from WT controls, however tetanic depression was greater, and quantal size during high-frequency stimulation and the size of the readily releasable pool (RRP) were decreased. At 24 months of age, quantal content was reduced in ChAT-ChR2-EYFP mice, which normalized synaptic depression despite smaller RRP. The effect of pancuronium on indirect evoked muscle twitch was not different between groups. These results indicate that an increase in the amount of acetylcholine per vesicle induces two distinct age-dependent homeostatic mechanisms compensating excessive acetylcholine release.