Revised cellular models for different phases of sensitization-related synaptic facilitation in Aplysia. The dashed lines depict pathways for which experimental evidence is currently lacking. (A) Short-term facilitation (STF). This phase lasts < 30 min. STF can be both induced and expressed presynaptically. (B) Intermediate-term facilitation (ITF). This phase lasts 90 min-to-3 hr. According to the model, ITF is induced postsynaptically, by release of Ca²⁺ from intracellular stores in the motor neuron, and expressed both pre- and postsynaptically. The presynaptic expression results from one or more retrograde signals, activated by postsynaptic Ca²⁺, which stimulate both PKA and PKC within the sensory neuron. (C) Long-term facilitation (LTF). LTF persists for ≥ 24 hr, and involves gene transcription, as well as both pre- and postsynaptic protein synthesis. Like ITF, LTF is induced postsynaptically, and expressed pre- and postsynaptically. LTF is triggered by repeated, spaced applications of 5-HT/sensitizing stimuli. A novel feature of the model in C is that it assumes that prolonged activation of presynaptic PKA, which leads to sensorin release and the translocation of PKA to the presynaptic nucleus, is triggered by elevated postsynaptic Ca²⁺, via retrograde signaling. In addition, for at least some forms of both LTF and ITF the retrograde signal may activate presynaptic PKC (Hu et al., 2007; Jin et al., 2004) as well as presynaptic PKA. From (Glanzman, 2007).

Presynaptic cellular model for short- and long-term sensitization in Aplysia. See the text for details. From (Kandel, 2001).