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 basis of their concentration requirement for 5HT, their activation and recovery kinetics, and their dependence on the relative contribution of different second messenger pathways. In addition, some of the facilitatory mechanisms activated by 5HT appear to be different depending upon the recent activation history of synaptic transmission from the SNs. In this study, we examined the concentration requirements of 5HT-induced facilitation of depressed and nondepressed synapses. 2. In isolated pleural-pedal ganglia, we produced facilitation of monosynaptic connections between tail SNs and motor neurons (MNs), using different concentrations of 5HT. As a measure of each preparation's greatest sensitivity to 5HT, we first determined the lowest 5HT concentration that produced increased excitability in the SNs ("threshold" 5HT). Then, in one series of experiments, we applied 5HT sequentially to the same synapse, first in the nondepressed and then in the depressed state. In a second series, we applied 5HT simultaneously to two SNs connecting to the same MN; one synapse was depressed, the other nondepressed. 3. In both series of experiments, we found that the 5HT concentration required to produce facilitation of depressed excitatory post-synaptic potentials (EPSPs) was invariably lower than the 5HT concentration that produced facilitation of nondepressed EPSPs. In the first series, 'threshold' 5HT (1.6 microM) was sufficient to facilitate the synapse in the depressed state, but not the nondepressed state. However, the nondepressed synapse could still be facilitated by higher concentrations of 5HT (10 microM). In the second series, increased excitability of SNs, facilitation of depressed synapses, and facilitation of nondepressed synapses were progressively recruited as a function of increasing 5HT concentration (4.1, 6.7, and 10-15 microM, respectively). 4. These data are consistent with previous studies suggesting that different cellular mechanisms contribute to the facilitation of depressed and nondepressed synapses. In addition, our results provide a way to experimentally separate the two processes and to analyze them simultaneously and independently. Taking advantage of this dissociation, in future experiments it may be possible to directly compare the relative contributions of different intracellular mechanisms to synaptic facilitation and to relate them to the degree of recent synaptic activation.