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

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.