TRANSIENT VERSUS PERSISTENT FUNCTIONAL AND STRUCTURAL-CHANGES ASSOCIATED WITH FACILITATION OF APLYSIA SENSORIMOTOR SYNAPSES ARE SECOND-MESSENGER DEPENDENT

increases in activity of both protein kinase A (PKA) and protein kinas e C (PKC) contribute to short-term facilitation of Aplysia sensorimoto r synapses evoked by serotonin (5-HT). We report here that increasing levels of cAMP in sensory neurons evokes increases in both synaptic ef ficacy and in the number of sensory neuron varicosities contacting the major axons of motor cell L7 at intermediate times (3 hr) that persis t for 24 hr. Treatment with phorbol esters results in a large transien t increase in synaptic efficacy that is accompanied by a large transie nt increase in the number of sensory neuron varicosities with the newe st varicosities most susceptible to elimination. The reversal of the s ynaptic facilitation and the structural changes does not appear to be the result of long-term inhibitory actions of persistent PKC activatio n by phorbol esters, since changes in;synaptic efficacy can be evoked by additional applications of either phorbol esters or 5-HT. The short -lived changes in structure evoked by phorbol esters occur in preexist ing sensory neurites and not by new growth, since increases in PKC act ivity with phorbol esters lead to reductions in neurite extension and to retractions by sensory neuron growth cones. The action of phorbol e sters on growth cone extension is reversible with washout. The results suggest that increases in PKA and PKC activities by 5-HT contribute t o short (minutes) and intermediate (hours) forms of facilitation of se nsorimotor synapses while increases in PKA activity also mediate long- term (days) maintenance of synaptic facilitation.