Requirement of Akt to mediate long-term synaptic depression in Drosophila.
Drosophila larval neuromuscular junction (NMJ) is a well established preparation enabling quantitative analyses of synaptic physiology at identifiable synapses. Here, we report the first characterization of synaptic long-term depression (LTD) at the Drosophila NMJ. LTD can be reliably induced by specific patterns of tetanic stimulation, and the level of LTD depends on both stimulus frequency and Ca2+ concentration. We provide evidence that LTD is likely a result of presynaptic changes. Through screening of targeted mutants with defects in memory or signal transduction pathways, we found that LTD is strongly reduced in the akt mutants. This defect can be rescued by acutely induced expression of the normal akt transgene, suggesting that altered LTD is not attributable to developmental abnormalities and that Akt is critical for the induction of LTD. Our study also indicates that the molecular mechanisms of LTD are distinct from that of short-term synaptic plasticity, because akt mutants showed normal short-term facilitation and posttetanic potentiation, whereas LTD was unaffected in mutants that exhibit defective short-term synaptic plasticity, such as dunce and rutabaga. The characterization of LTD allows genetic analysis of the molecular mechanisms of long-term synaptic plasticity in Drosophila and provides an additional assay for studying functions of genes pertaining to synaptic and behavioral plasticity.
Guo
Hui-Fu
HF
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Zhong
Yi
Y
D000818:Animals; D002118:Calcium / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology; D004330:Drosophila / Q000254:growth & development; D007814:Larva / Q000502:physiology; D017998:Leukotriene D4 / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000502:physiology*
D017998:Leukotriene D4; D051057:Proto-Oncogene Proteins c-akt; D002122:Calcium Chloride; D002118:Calcium