INVOLVEMENT OF PRESYNAPTIC AND POSTSYNAPTIC MECHANISMS IN A CELLULAR ANALOG OF CLASSICAL-CONDITIONING AT APLYSIA SENSORY-MOTOR NEURON SYNAPSES IN ISOLATED CELL-CULTURE

Temporal pairing of presynaptic activity and serotonin produces enhanc ed facilitation at Aplysia sensory-motor neuron synapses (pairing-spec ific facilitation), which may contribute to classical conditioning of the gill and siphon withdrawal reflex. This cellular analog of conditi oning is thought to involve Ca2+ priming of the cAMP pathway in the se nsory neurons. Consistent with that idea, we have found that pairing-s pecific facilitation by serotonin is greatly reduced by presynaptic in jection of a slow Ca2+ chelator or a specific inhibitor of cAMP-depend ent protein kinase and is accompanied by a transient increase in the f requency but by no change in the amplitude of spontaneous, miniature E PSPs. However, like post-tetanic potentiation (PTP) and long-term pote ntiation (LTP) at these synapses, pairing-specific facilitation is als o greatly reduced by postsynaptic injection of a rapid Ca2+ chelator o r by postsynaptic hyperpolarization during training, although postsyna ptic hyperpolarization has no effect on the increase in frequency or o n the amplitude of spontaneous EPSPs. These results suggest that pairi ng-specific facilitation by serotonin involves Hebbian postsynaptic as well as non-Hebbian presynaptic components that interact in some way, perhaps via retrograde signaling, to specifically enhance evoked, syn chronized release of transmitter.