PHARMACOLOGICAL AND KINETIC CHARACTERIZATION OF 2 FUNCTIONAL CLASSES OF SEROTONERGIC MODULATION IN APLYSIA SENSORY NEURONS

1. Modulation of mechanoafferent sensory neurons (SNs) by the neurotra nsmitter serotonin (5HT) plays a significant role in behavioral sensit ization of several withdrawal reflexes in Aplysia. The modulatory effe cts of 5HT on these SNs include increased excitability, increased inpu t resistance, action potential broadening and increased synaptic trans mission. Based on a previously described dissociation of some of these modulatory effects, revealed with the 5HT-receptor antagonist, cyproh eptadine, we investigated whether a similar dissociation could be foun d by systematically varying the concentration of the endogenous agonis t, 5HT. 2. We first applied a range of 5HT concentrations to isolated pleural/pedal ganglia (containing tail SNs and tail motor neurons, res pectively), and measured the magnitude of 5HT-induced modulation of sp ike broadening and increased excitability. The resulting dose-response curve showed that both forms of modulation increase monotonically as a function of 5HT concentration, but that excitability has a lower thr eshold for modulation by 5HT than does spike duration. 3. We further c haracterized the modulatory effects of 5HT on Aplysia SNs by comparing the time course of onset of modulation by 5HT and the time course of recovery after washout. Independent of 5HT concentration, modulation o f excitability increases rapidly in the presence of 5HT and recovers r apidly (<3 min) after washout. Similarly, input resistance increases a nd recovers rapidly, mirroring the profile of increased excitability. However, modulation of spike duration exhibits two profiles, dependent on 5HT concentration. Low concentrations of 5HT (0.5 and 1 mu M) indu ce a rapid-onset and transient-recovery form of spike broadening, whic h resembles the kinetics of increased excitability and increased input resistance. Higher concentrations of 5HT (2.5 and 5 mu M) induce a mo re slowly developing and prolonged-recovery form of spike broadening ( >9 min). At these higher concentrations, the recovery profile for prol onged spike broadening is significantly different from those observed for both increased excitability and increased input resistance. 4. We next compared the relationship between spike broadening and short-term synaptic facilitation. We found that significant facilitation of syna ptic transmission requires a high 5HT concentration, which is comparab le with that required to induce prolonged spike broadening. Similarly, the recovery profiles for spike broadening and synaptic facilitation are strikingly similar, recovering in parallel. 5. Our experiments sho w that the modulatory effects of 5HT in the tail SNs can be dissociate d both by their sensitivity to different concentrations of 5HT and by their kinetics of serotonergic modulation. Based on these results, tog ether with extensive evidence from other laboratories, we propose that the short-term modulatory effects of 5HT fall into two distinct funct ional classes. The first class, which includes excitability, input res istance, and transient spike broadening, has a low threshold for 5HT m odulation and recovers rapidly. The second class, which includes prolo nged spike broadening and short-term synaptic facilitation, has a high er threshold for modulation and recovers more slowly. It now will be o f interest to determine the functional contribution of each of these c lasses to different aspects of sensitization.