Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation in Aplysia

The induction of different phases of memory depends on the amount and patterning of training, raising the question of whether specific training patterns engage different cellular mechanisms and whether these mechanisms operate in series or in parallel. We examined these questions by using a cellular model of memory formation: facilitation of the tail sensory neuron-motor neuron synapses by serotonin (5-hydroxytryptamine, 5-HT) in the CNS of Aplysia. We studied facilitation in two temporal domains: intermediate-term facilitation (1.5-3 h) and long-term facilitation (LTF, >24 h). Both forms can be induced by using several different temporal and spatial patterns of 5-HT, including (i) repeated, temporally spaced pulses of 5-HT to both the sensory neuron soma and the sensory neuron-motor neuron synapse, and (ii) temporally asymmetric exposure of 5-HT to the soma and synapse under conditions in which neither exposure alone induces LTF. We first examined the protein and RNA synthesis requirements for LTF induced by these two patterns and found that asymmetric (but not repeated) 5-HT application induced LTF that required postsynaptic protein and RNA synthesis. We next focused on the patterning and protein synthesis requirements for intermediate-term facilitation. We found that intermediate-term facilitation (i) is induced locally at the synapse, (ii) requires multiple pulses of 5-HT, and (iii) requires synaptic protein synthesis. Our findings show that different temporal and spatial patterns of 5-HT induce specific temporal phases of long-lasting facilitation in parallel by engaging different cellular and molecular mechanisms.