DEVELOPMENT OF SHORT-TERM HETEROSYNAPTIC FACILITATION AT APLYSIA SENSORIMOTOR SYNAPSES IN-VITRO IS ACCOMPANIED BY CHANGES IN THE FUNCTIONALEXPRESSION OF PRESYNAPTIC SEROTONIN RECEPTORS

1. The sensorimotor synapse of Aplysia expresses various shortlasting changes in synaptic efficacy including homosynaptic depression (HSD) a nd heterosynaptic facilitation by serotonin (5-HT) either at nondepres sed sensory neuron (SN) synaptic connections or at SN synaptic connect ions first depressed by HSD. We examined the temporal sequence of expr ession for these three forms of synaptic plasticity as synaptic connec tions between SN and target motor cell L7 were reestablished and stabi lized in cell culture. The same cultures were reexamined at different time points. 2. We found that only HSD and facilitation of nondepresse d synapses were expressed at ''mature'' levels on day 1 in culture, wh ereas facilitation of depressed connections was significantly weaker o n day 1 than the facilitation evoked on day 4. 3. The late expression of 5-HT facilitation of depressed SN synaptic connections was not a re sult of a reduced capacity of two kinases activated by 5-HT (protein k inase A and protein kinase C) to evoke facilitation. Direct activation of the kinases with either cyclic AMP or phorbol esters evoked the sy naptic faciltation both on day 1 and day 4. 4. The late expression of 5-HT facilitation of depressed SN synaptic connections was correlated with the late functional expression of receptors sensitive to 5-HT ant agonists cyproheptidine or methiothepin. Both antagonists significantl y interfered with 5-HT facilitation on day 4, but both had little effe ct on 5-HT facilitation of the same cultures examined on day 1. 5. Unl ike the properties of SNs in the intact nervous system, both antagonis ts reduced significantly the excitability changes evoked by 5-HT when the SNs were plated either alone or with target cell L11 that fails to induce synapse formation. When cultured with L7, however, both antago nists evoked little change in 5-HT excitability. In the presence of L7 , the SNs expressed the phenotype more typical of SNs in the intact ne rvous system. 6. The results suggest that target interactions not only influence the formation of chemical connections but they also may reg ulate the acquisition of specific plastic properties by the presynapti c neuron including the functional expression of receptors for neuromod ulators.