Role of cAMP in the Short-Term Modulation of a Neuromuscular System in Aplysia

Neuromuscular synapses in buccal muscle I3a of Aplysia are modulated by the small cardioactive peptide (SCP), a peptide cotransmitter that is intrinsic to the motor neurons, and by serotonin (5-HT) released from modulatory neurons that are extrinsic to the motor circuit. Although the modulation of excitatory junction potentials (EJPs) and contractions by 5-HT and SCP has been studied extensively in this muscle, little is known about the mechanisms that underlie the modulation. 5-HT and SCP, at 1 μM, were found to potently increase the level of cAMP in I3a. Therefore we investigated whether the activation of the cAMP pathway was sufficient to modulate EJPs and contractions. The direct activation of adenylyl cyclase with forskolin increased the level of cAMP, facilitated EJPs, and potentiated contractions. Indeed, the short-term effects of forskolin were very similar to all aspects of the short-term effects of 5-HT and SCP. Membrane-permeable cAMP analogues also mimicked the effects of 5-HT and SCP on EJPs and contractions. However, it seems likely that some effects of 5-HT are also mediated through other second-messenger pathways because low concentrations of 5-HT modulate EJPs and contractions but do not significantly increase cAMP levels in I3a. It is possible that lower concentrations of 5-HT function through receptors linked to protein kinase C (PKC) because phorbol, an activator of PKC, modulated EJPs and contractions without increasing the levels of cAMP. In conclusion, we provide evidence that pharmacological agents that activate the cAMP pathway mimicked most of the effects of 5-HT or SCP and that more than one second-messenger system appears to be involved in the modulation of the I3a neuromuscular system.

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Serotonergic Neurons Differentially Modulate the Efficacy of Two Motor Neurons Innervating the Same Muscle Fibers in Aplysia

Journal of Neurophysiology ◽

10.1152/jn.1998.80.2.647 ◽

1998 ◽

Vol 80 (2) ◽

pp. 647-655 ◽

Cited By ~ 17

Author(s):

Lyle E. Fox ◽

Philip E. Lloyd

Keyword(s):

Feeding Behavior ◽

Motor Neurons ◽

Muscle Fibers ◽

Short Term ◽

Serotonergic Neurons ◽

Anterior Portion ◽

Excitatory Junction Potentials ◽

Evoked Contractions ◽

Stimulation Of ◽

Short Term Effects

Fox, Lyle E. and Philip E. Lloyd. Serotonergic neurons differentially modulate the efficacy of two motor neurons innervating the same muscle fibers in Aplysia. J. Neurophysiol. 80: 647–655, 1998. Feeding behavior in Aplysia shows substantial plasticity. An important site for the generation of this plasticity is the modulation of synaptic transmission between motor neurons and the buccal muscles that generate feeding movements. We have been studying this modulation in the anterior portion of intrinsic buccal muscle 3 (I3a), which is innervated by two excitatory motor neurons and identified serotonergic modulatory neurons, the metacerebral cells (MCCs). We have shown previously that serotonin (5-HT) applied selectively to the muscle potently modulates excitatory junction potentials (EJPs) and contractions. All the effects of 5-HT were persistent, lasting many hours after wash out. We examined whether the release of endogenous 5-HT from the MCC could produce effects similar to the application of 5-HT. Stimulation of the MCCs did produce similar short-term effects to the application of 5-HT. MCC stimulation facilitates EJPs, potentiates contractions, and decreases the latency between the onset of a motor neuron burst and the onset of the evoked contraction. The effects of MCC stimulation reached a maximum at quite low firing frequencies, which were in the range of those previously recorded during feeding behavior. The maximal effects were similar to those produced by superfusion with ∼0.1 μM 5-HT. Although the effects of MCC stimulation on EJPs were persistent, they were less persistent than the effects of 0.1 μM 5-HT. Mechanisms that may account for differences in the persistence between released and superfused 5-HT are discussed. Thus activity in the MCCs has dramatic short-term effects on the behavioral output of motor neurons, increasing the amplitude and relaxation rate of contractions evoked by both B3 and B38 and shifting the temporal relationship between B38 bursts and evoked contractions.

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Use of the perifusion technique on rat thyroid fragments in the study of thyroid hormone secretion: short-term effects of thyrotrophin, theophylline and glucagon

Journal of Endocrinology ◽

10.1677/joe.0.1020043 ◽

1984 ◽

Vol 102 (1) ◽

pp. 43-NP ◽

Cited By ~ 7

Author(s):

J. R. Attali ◽

D. Darnis ◽

P. Valensi ◽

C. Weisselberg ◽

J. Sebaoun

Keyword(s):

Thyroid Hormone ◽

Dose Response ◽

Linear Correlation ◽

Hormone Secretion ◽

Kinetic Studies ◽

Dynamic Effects ◽

Short Term ◽

Pharmacological Agents ◽

Rat Thyroid ◽

Short Term Effects

ABSTRACT Perifusion of rat thyroid fragments was performed to study short-term effects of TSH, theophylline and glucagon on thyroid hormone secretion. This technique proved to be relatively convenient and sensitive, and gave reproducible results for at least 3 h, permitting precise kinetic studies of response to hormonal and pharmacological agents without any interference. There was a significant (P < 0·001) linear correlation between the log TSH concentrations over the range 20–150 mu./ml and thyroid response. A second stimulation, using the same concentration of TSH, did not differ from the first stimulation if they were separated by an active 'washing' period of only 15 min. Theophylline also had a stimulating effect and like TSH induced an early release of the hormone fraction with a peak between 2 and 4 min, but it did not potentiate the TSH effect. Perifusion of rat thyroid fragments was found to be a useful tool for analysing dynamic effects of various substances. These effects were significant for periods of time as short as 20 min. Each thyroid preparation could be used a second time for another pharmacological or hormonal test. Our preliminary results also suggested that there was a direct glucagon effect on thyroid hormone secretion with a dose–response correlation. J. Endocr. (1984) 102, 43–48

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