Drosophila larval neuromuscular junction's responses to reduction of cAMP in the nervous system

We investigated the effects of chronically lowered cyclic adenosine monopho sphate (cAMP) on the morphology and physiology of the Drosophila larval neu romuscular junction, using two fly lines in which cAMP was significantly lo wer than normal in the nervous system: (a) transgenic dies in which the dun ce (dnc) gene product was overexpressed in the nervous system, and (b) flie s mutant for the rutabaga gene (rut(1)) which have reduced adenylyl cyclase activity. In comparison with controls, larvae with reduced cAMP exhibited a smaller number of synaptic varicosities. This effect was more pronounced in transgenic larvae, in which the reduction of neural cAMP was more pronou nced. Synaptic transmission was also reduced in both cases, as evidenced by smaller excitatory junctional potentials (EJPs), Synaptic currents recorde d from individual synaptic varicosities of the neuromuscular junction indic ated almost normal transmitter release properties in transgenic larvae and a modest impairment in rut(1) larvae. Thus, reduction in EJP amplitude in t ransgenic larvae is primarily due to reduced innervation, while in rut(1) l arvae it is attributable to the combined effects of reduced innervation and a mild impairment of transmitter release. We conclude that the major effec t of chronically lowered cAMP is reduction of innervation rather than impai rment of transmitter release properties. (C) 1999 John Wiley & Sons, Inc.