A novel function for serotonin-mediated short-term facilitation in Aplysia: Conversion of a transient, cell-wide homosynaptic Hebbian plasticity intoa persistent, protein synthesis-independent synapse-specific enhancement

Studies of sensitization and classical conditioning of the gill-withdrawal reflex in Aplysia have shown that the synaptic connections between identifi ed glutamatergic sensory neurons and motor neurons can be enhanced in one o f two ways: by a heterosynaptic (modulatory input-dependent) mechanism that gives rise with repetition to long-term facilitation and by a homosynaptic (activity dependent) mechanism that gives rise with repetition to a facili tation that is partially blocked by 2-amino-5-phosphonovaleric acid and by injection of 1.2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) i nto the postsynaptic cell and is similar to long-term potentiation in the h ippocampus. We here have examined how these two forms of facilitation inter act at the level of an individual synaptic connection by using a culture pr eparation consisting of a single bifurcated sensory neuron that forms indep endent synaptic contacts with each of two spatially separated motor neurons . We find that the homosynaptic facilitation produced by a train of action potentials is cell wide and is evident at all of the terminals of the senso ry neuron. By contrast, the heterosynaptic facilitation mediated by the mod ulatory transmitter serotonin (5-HT) can operate at the level of a single s ynapse. Homosynaptic activation gives rise to only a transient facilitation lasting a few hours, even when repeated in a spaced manner. The heterosyna ptic facilitation produced by a single pulse of 5-HT, applied to one termin al of the sensory neuron, also lasts only minutes. However, when one or mor e homosynaptic trains of spike activity are paired with even a single pulse of 5-HT applied to one of the two branches of the sensory neuron, the comb ined actions lead to a selective enhancement in synaptic strength only at t he 5-HT-treated branch that now lasts more than a day, and thus amplifies, by more than 20-fold, the duration of the individually produced homo-and he terosynaptic facilitation. This form of synapse-specific facilitation has u nusual long-term properties. It does not require protein synthesis, nor is it accompanied by synaptic growth.