Role of cAMP cascade in synaptic stability and plasticity: Ultrastructuraland physiological analyses of individual synaptic boutons in Drosophila memory mutants

Mutations of the genes rutabaga (rut) and dunce (dnc) affect the synthesis and degradation of cAMP, respectively, and disrupt learning in Drosophila. Combined ultrastructural analysis and focal electrophysiological recording in the larval neuromuscular junction revealed a loss of stability and fine tuning of synaptic structure and function in both mutants. Increased ratios of docked/undocked vesicles and poorly defined synaptic specializations ch aracterized dnc synapses. In contrast, rut boutons possessed fewer, althoug h larger, synapses with lower proportions of docked vesicles. At reduced Ca 2+ levels, decreased quantal content coupled with an increase in failure ra te was seen in rut boutons and reduced pair-pulse facilitation were found i n both rut and dnc mutants. At physiological Ca2+ levels, strong enhancemen t, instead of depression, in evoked release was observed in some dnc and ru t boutons during 10 Hz tetanus. Furthermore, increased variability of synap tic transmission, including fluctuation and asynchronicity of evoked releas e, paralleled an increase in synapse size variation in both dnc and rut bou tons, which might impose problems for effective signal processing in the ne rvous system. Pharmacological and genetic studies indicated broader ranges of physiological alteration by dnc and rut mutations than either the acute effects of cAMP analogs or the available mutations that affect cAMP-depende nt protein kinase (PKA) activity. This is consistent with previous reports of more severe learning defects in dnc and rut mutations than these PKA mut ants and allows identification of the phenotypes involving long-term develo pmental regulation and those conferred by PKA.