Identification of Nicotinic Acetylcholine Receptor Recycling and Its Role in Maintaining Receptor Density at the Neuromuscular Junction In Vivo

• Published in: The Journal of neuroscience Vol. 25; no. 43; pp. 9949 - 9959
• Main Authors: Bruneau, Emile, Sutter, David, Hume, Richard I, Akaaboune, Mohammed
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 26.10.2005; Society for Neuroscience
• Subjects: Animals; Biotin - metabolism; Bungarotoxins - pharmacokinetics; Development/Plasticity/Repair; Diagnostic Imaging - methods; Female; Fluorescent Dyes - metabolism; Mice; Neuromuscular Junction - metabolism; Receptor Aggregation - drug effects; Receptor Aggregation - physiology; Receptors, Nicotinic - metabolism; Streptavidin - metabolism; Synapses - metabolism; Time Factors
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3169-05.2005

In the CNS, receptor recycling is critical for synaptic plasticity; however, the recycling of receptors has never been observed at peripheral synapses. Using a novel imaging technique, we show here that nicotinic acetylcholine receptors (AChRs) recycle into the postsynaptic membrane of the neuromuscular junction. By sequentially labeling AChRs with biotin-bungarotoxin and streptavidin-fluorophore conjugates, we were able to distinguish recycled, preexisting, and new receptor pools at synapses in living mice. Time-lapse imaging revealed that recycled AChRs were incorporated into the synapse within hours of initial labeling, and their numbers increased with time. At fully functional synapses, AChR recycling was robust and comparable in magnitude with the insertion of newly synthesized receptors, whereas chronic synaptic activity blockade nearly abolished receptor recycling. Finally, using the same sequential labeling method, we found that acetylcholinesterase, another synaptic component, does not recycle. These results identify an activity-dependent AChR-recycling mechanism that enables the regulation of receptor density, which could lead to rapid alterations in synaptic efficacy.