A cellular mechanism of classical conditioning in Aplysia.

The defensive siphon and gill withdrawal of Aplysia is a simple reflex, mediated by a well-defined neural circuit, that exhibits sensitization in response to strong stimulation of the tail. The siphon withdrawal reflex also exhibits classical conditioning when a weak stimulus to the siphon or mantle shelf (the conditioned stimulus or CS) is paired with a shock to the tail (the unconditioned stimulus or US). Cellular studies indicate that the mechanism of this conditioning shares aspects of the mechanism of sensitization of the reflex: presynaptic facilitation due to a cAMP-mediated decrease in K+ current and consequent broadening of action potentials in the sensory neurones. Thus, tail shock (the US) produces greater facilitation of the monosynaptic EPSP from a sensory to a motor neurone if the shock is immediately preceded by spike activity in the sensory neurone than if it occurs without spike activity (sensitization), or if the shock and spike activity are presented in a specifically unpaired pattern. This activity-dependent amplification of facilitation involves a greater broadening of action potentials in paired than in unpaired sensory neurones and appears to be due to a greater depression of the same serotonin- and cAMP-sensitive K+ current involved in sensitization. These results indicate that a mechanism of classical conditioning of the withdrawal reflex is an elaboration of the mechanism underlying sensitization. By analogy, the mechanisms of higher-order features of learning, such as the effect of contingency, may be built from combinations of the molecular mechanisms of these simple forms of learning.