Requirement of protein kinase B (akt) for long-term depression at the Drosophila neuromuscular junction. H. Guo , Y. Zhong. Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

   Several forms of short-term synaptic plasticity have been reported at the Drosophila neuromuscular junction (NMJ), including paired-pulse facilitation, short-term facilitation, augmentation and post-titanic potentiation etc. Genetic dissection has provided insights to the mechanism of synaptic transmission and plasticity, and vise versa, analyses of these forms of synaptic plasticity have helped elucidating the function of learning and memory-related genes in synaptic transmission and plasticity.
  Here we report a form of long-term synaptic plasticity at the Drosophila NMJ. A titanic stimulation (30 Hz, 20 sec) induced a long-term depression (LTD) of evoked-synaptic currents (EJC), which lasts at least for 1 hr. The amplitude of EJC was reduced to 30-50% after the titanic stimulation. The induction of LTD is calcium concentration dependent, which can be induced at 0.35-0.4 mM Ca2+, but not at 0.7 mM (or higher concentration) Ca2+, and it is expressed on specific muscle fibers (e.g. #13 but not on #6). Quantal analyses revealed that the quantal size was not changed, whereas the quantal content was reduced to less than 50%. In addition, direct application of glutamate-induced synaptic currents did not change significantly after the titanic stimulation, suggesting a presynaptic mechanism of this plasticity.
  Genetic analyses indicate protein kinase B (Akt), which is a major target of PI-3 kinase, is required for this long-term depression. The mutations of akt gene largely attenuated the depression. We are currently conducting more detailed analyses of the role of akt in this LTD. This long-term plasticity can be used as a model for studying gene function and signal transduction underlying synaptic plasticity and learning and memory mechanism. Supported by: NIH grant R01-NS34779 to Y.Z.