Rapid and reversible effects of activity on acetylcholine receptor densityat the neuromuscular junction in vivo

Quantitative fluorescence imaging was used to study the regulation of acety lcholine receptor (AChR) number and density at neuromuscular junctions in L iving adult mice. At fully functional synapses, AChRs have a half-life of a bout 14 days. However, 2 hours after neurotransmission was blocked, the hal f-life of the AChRs was now Less than a day; the rate was 25 times faster t han before. Most of the Lost receptors were not quickly replaced. Direct mu scle stimulation or restoration of synaptic transmission inhibited this pro cess. AChRs that were removed from nonfunctional synapses resided for hours in the perijunctional membrane before being Locally internalized. Disperse d AChRs could also reaggregate at the junction once neurotransmission was r estored. The rapid and reversible alterations in AChR density at the neurom uscular junction in vivo parallel changes thought to occur in the central n ervous system at synapses undergoing potentiation and depression.