THRESHOLD SEROTONIN CONCENTRATION REQUIRED TO PRODUCE SYNAPTIC FACILITATION DIFFERS FOR DEPRESSED AND NONDEPRESSED SYNAPSES IN APLYSIA SENSORY NEURONS

1. The modulatory actions produced by the neurotransmitter serotonin ( 5HT) in Aplysia sensory neurons (SNs) can be distinguished on the basi s of their concentration requirement for 5HT, their activation and rec overy kinetics, and their dependence on the relative contribution of d ifferent second messenger pathways. In addition, some of the facilitat ory mechanisms activated by 5HT appear to be different depending upon the recent activation history of synaptic transmission from the SNs. I n this study, we examined the concentration requirements of 5HT-induce d facilitation of depressed and nondepressed synapses. 2. In isolated pleural-pedal ganglia, we produced facilitation of monosynaptic connec tions between tail SNs and motor neurons (MNs), using different concen trations of 5HT. As a measure of each preparation's greatest sensitivi ty to 5HT, we first determined the lowest 5HT concentration that produ ced increased excitability in the SNs ( ''threshold'' 5HT). Then, in o ne series of experiments, we applied 5HT sequentially to the same syna pse, first in the nondepressed and then in the depressed state. In a s econd series, we applied 5HT simultaneously to two SNs connecting to t he same MN; one synapse was depressed, the other nondepressed. 3. In b oth series of experiments, we found that the 5HT concentration require d to produce facilitation of depressed excitatory postsynaptic potenti als (EPSPs) was invariably lower than the 5HT concentration that produ ced facilitation of nondepressed EPSPs. In the first series, 'threshol d' 5HT (1.6 mu M) was sufficient to facilitate the synapse in the depr essed state, but not the nondepressed state. However, the nondepressed synapse could still be facilitated by higher concentrations of 5HT (1 0 mu M). In the second series, increased excitability of SNs, facilita tion of depressed synapses, and facilitation of nondepressed synapses were progressively recruited as a function of increasing 5HT concentra tion (4.1, 6.7, and 10-15 mu M, respectively). 4. These data are consi stent with previous studies suggesting that different cellular mechani sms contribute to the facilitation of depressed and nondepressed synap ses. In addition, our results provide a way to experimentally separate the two processes and to analyze them simultaneously and independentl y. Taking advantage of this dissociation, in future experiments it may be possible to directly compare the relative contributions of differe nt intracellular mechanisms to synaptic facilitation and to relate the m to the degree of recent synaptic activation.