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1. Modulation of mechanoafferent sensory neurons (SNs) by the neutrotransmitter serotonin (5HT) plays a significant role in behavioral sensitization of several withdrawal reflexes in Aplysia. The modulatory effects of 5HT on these SNs include increased excitability, increased input resistance, action potential broadening, and increased synaptic transmission. Based on a previously described dissociation of some of these modulatory effects, revealed with the 5HT-receptor antagonist, cyproheptadine, we investigated whether a similar dissociation could be found by systematically varying the concentration of the endogenous agonist, 5HT. 2. We first applied a range of 5HT concentrations to isolated pleural/pedal ganglia (containing tail SNs and tail motor neurons, respectively), and measured the magnitude of 5HT-induced modulation of spike 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 threshold for modulation by 5HT than does spike duration. 3. We further characterized 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 of excitability increases rapidly in the presence of 5HT and recovers rapidly (< 3 min) after washout. Similarly, input resistance increases and 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 microM) induce a rapid-onset and transient-recovery form of spike broadening, which resembles the kinetics of increased excitability and increased input resistance. Higher concentrations of 5HT (2.5 and 5 microM) induce a more slowly developing and prolonged-recovery form of spike broadening (> 9 min). At these higher concentrations, the recovery profile for prolonged 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 synaptic transmission requires a high 5HT concentration, which is comparable 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 show that the modulatory effects of 5HT in the tail SNs can be dissociated both by their sensitivity to different concentrations of 5HT and by their kinetics of serotonergic modulation. Based on these results, together with extensive evidence from other laboratories, we propose that the short-term modulatory effects of 5HT fall into two distinct functional classes. The first class, which includes excitability, input resistance, and transient spike broadening, has a low threshold for 5HT modulation and recovers rapidly. The second class, which includes prolonged spike broadening and short-term synaptic facilitation, has a higher threshold for modulation and recovers more slowly. It now will be of interest to determine the functional contribution of each of these classes to different aspects of sensitization.

We have addressed whether mechanisms of adult plasticity reflect conserved forms of developmental processes by comparing the effects of serotonin (5HT) in juvenile and adult Aplysia sensory neurons. We show that the effects of 5HT can be dissociated into two functional classes which (i) contribute differentially to short- and long-term synaptic plasticity in adults and (ii) emerge differentially during development. We propose a model in which one class of mechanism mediates structural changes early in development and is retained in the adult to subserve long-term memory, while the second class develops late and contributes only to short-term memory in the adult.

The renin-angiotensin and atriopeptin systems play important roles in the regulation of volume and fluid homeostasis. The two systems have opposing physiologic actions in a number of tissues. Experiments were performed to determine whether there were differences in the developmental expression of the genes for renin, angiotensinogen, and atriopeptin. Using RNA dot blot analysis, we compared levels of gene activity for renin, angiotensinogen, and atriopeptin in right atria, left atria, right ventricle, and left ventricle, from 18-day in ovum and 10-day old White Leghorn chicks. In 18-day embryonic chick heart there was expression of atriopeptin mRNA predominantly in the left and right ventricles. At this age, atriopeptin message was expressed in all four cardiac chambers, left ventricle greater than right ventricle greater than right atria greater than left atria. Renin and angiotensinogen mRNA was expressed in all cardiac chambers with reduced expression in left atria. In 10-day old chicks, renin, angiotensinogen, and atriopeptin mRNA was expressed in atrial tissue with right atria greater than left atria, with no detectable expression in left ventricle, right ventricle, or skeletal muscle. Beta actin was expressed in all four cardiac chambers and skeletal muscle, and was used to normalize signals. Cardiac expression of the genes for renin and angiotensinogen during embryogenesis suggests that the renin-angiotensin system may be involved in the growth and development of the myocardium.