New tricks for an old slug: the critical role of postsynaptic mechanisms in learning and memory in Aplysia

Abstract

The marine snail Aplysia has served for more than four decades as an important model system for neurobiological analyses of learning and memory. Until recently, it has been believed that learning and memory in Aplysia were due predominately, if not exclusively, to presynaptic mechanisms. For example, two nonassociative forms of learning exhibited by Aplysia, sensitization and dishabituation of its defensive withdrawal reflex, have been previously ascribed to presynaptic facilitation of the connections between sensory and motor neurons that mediate the reflex. Recent evidence, however, indicates that postsynaptic mechanisms play a far more important role in learning and memory in Aplysia than formerly appreciated. In particular, dishabituation and sensitization depend on a rise in intracellular Ca(2+) in the postsynaptic motor neuron, postsynaptic exocytosis, and modulation of the functional expression of postsynaptic AMPA-type glutamate receptors. In addition, the expression of the persistent presynaptic changes that occur during intermediate- and long-term dishabituation and sensitization appears to require retrograde signals that are triggered by elevated postsynaptic Ca(2+). The model for learning-related synaptic plasticity proposed here for Aplysia is similar to current mammalian models. This similarity suggests that the cellular mechanisms of learning and memory have been highly conserved during evolution.

Fig. 1

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

Fig. 2

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).