| Abstract: | Activity‐dependent selective reduction of synaptic efficacy is expressed in an in vitro system involving mouse spinal cord and muscle cells. Thrombin or electrical stimulation of the innervating axons induces a decrease in neuromuscular synapse strength, and a specific thrombin inhibitor, hirudin, blocks the electrically evoked down‐regulation of synapse effectiveness. We further demonstrate that a thrombin receptor‐activating peptide (TRAP), SFLLRNPNDKYEPF, produces a decrement of synapse strength. Both TRAP and electrically evoked synapse decrement are prevented by the specific protein kinase C blocker calphostin C, and the TRAP‐evoked synapse decrement is unaffected by a specific protein kinase A blocker, H‐89. Thus, we propose that muscle activity, thrombin release, and thrombin receptor and PKC activation are initial steps in the process of the activity‐dependent synapse reduction expressed in our system. © 1999 John Wiley & Sons, Inc. J Neurobiol 38: 369–381, 1999 |
