Phosphorylation and local presynaptic protein synthesis in calcium- and calcineurin-dependent induction of crayfish long-term facilitation.

Long-term facilitation at the crayfish opener muscle is elicited by prolonged high frequency stimulation, and arises from an increase in functional active zones, resulting in increased transmitter release. LTF induction depends critically upon presynaptic calcium accumulation and calcineurin (PP2B) activity. The protein synthesis dependence of this synaptic strengthening was investigated. LTF occurred without transcription, but the translation inhibitors cycloheximide and anisomycin, or local presynaptic injection of mRNA cap analog m7GpppG, impaired LTF expression. Both MAP kinase and phosphatidylinositol 3-OH kinase (PI3K) activation are implicated in this rapamycin-sensitive synaptic potentiation. This study defines an important role for protein synthesis in the expression of activity-dependent plasticity, and provides mechanistic insight for the induction of this process at presynaptic sites.