Role of cAMP cascade in synaptic stability and plasticity: ultrastructural and 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 characterized dnc synapses. In contrast, rut boutons possessed fewer, although larger, synapses with lower proportions of docked vesicles. At reduced Ca(2+) levels, decreased quantal content coupled with an increase in failure rate was seen in rut boutons and reduced pair-pulse facilitation were found in both rut and dnc mutants. At physiological Ca(2+) levels, strong enhancement, instead of depression, in evoked release was observed in some dnc and rut boutons during 10 Hz tetanus. Furthermore, increased variability of synaptic transmission, including fluctuation and asynchronicity of evoked release, paralleled an increase in synapse size variation in both dnc and rut boutons, which might impose problems for effective signal processing in the nervous 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-dependent protein kinase (PKA) activity. This is consistent with previous reports of more severe learning defects in dnc and rut mutations than these PKA mutants and allows identification of the phenotypes involving long-term developmental regulation and those conferred by PKA.
Renger
J J
JJ
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52240, USA.
Ueda
A
A
Atwood
H L
HL
Govind
C K
CK
Wu
C F
CF
D000483:Alleles; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002452:Cell Count; D000242:Cyclic AMP / Q000502:physiology*; D004331:Drosophila melanogaster; D004558:Electric Stimulation; D007814:Larva; D008568:Memory / Q000502:physiology*; D008854:Microscopy, Electron; D009132:Muscles / Q000294:innervation; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology*; D010641:Phenotype; D017729:Presynaptic Terminals / Q000502:physiology* / Q000648:ultrastructure*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure*
D000242:Cyclic AMP