A retrograde signal is involved in activity-dependent remodeling at a C-elegans neuromuscular junction

We have characterized how perturbations of normal synaptic activity influen ce the morphology of cholinergic SAB motor neurons that innervate head musc le in C. elegans. Mutations disrupting components of the presynaptic releas e apparatus, acetylcholine (ACh) synthesis or ACh loading into synaptic ves icles each induced sprouting of SAB axonal processes. These sprouts usually arose in the middle of the normal innervation zone and terminated with a s ingle presynaptic varicosity. Sprouting SAB neurons with a similar morpholo gy were also observed upon reducing activity in muscle, either by using mut ants lacking a functional nicotinic ACh receptor subunit or through muscle- specific expression of a gain-of function potassium channel, Analysis of te mperature-sensitive mutants in the choline acetyltransferase gene revealed that the sprouting response to inactivity was developmentally regulated; re duction of synaptic activity in early larval stages, but not in late larval stages, induced both sprouting and addition of varicosities. Our results i ndicate that activity levels regulate the structure of certain synaptic con nections between nerve and muscle in C. elegans. One component of this regu latory machinery is a retrograde signal from the postsynaptic cell that med iates the formation of synaptic connections.