Bao_1998_J.Neurosci_18_458

Temporal pairing of presynaptic activity and serotonin produces enhanced facilitation at Aplysia sensory-motor neuron synapses (pairing-specific facilitation), which may contribute to classical conditioning of the gill and siphon withdrawal reflex. This cellular analog of conditioning is thought to involve Ca2+ priming of the cAMP pathway in the sensory neurons. Consistent with that idea, we have found that pairing-specific facilitation by serotonin is greatly reduced by presynaptic injection of a slow Ca2+ chelator or a specific inhibitor of cAMP-dependent protein kinase and is accompanied by a transient increase in the frequency but by no change in the amplitude of spontaneous, miniature EPSPs. However, like post-tetanic potentiation (PTP) and long-term potentiation (LTP) at these synapses, pairing-specific facilitation is also greatly reduced by postsynaptic injection of a rapid Ca2+ chelator or by postsynaptic hyperpolarization during training, although postsynaptic hyperpolarization has no effect on the increase in frequency or on the amplitude of spontaneous EPSPs. These results suggest that pairing-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, synchronized release of transmitter.