Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites

Abstract

The neuroendocrine bag cells in the abdominal ganglion of Aplysia generate a long-lasting synchronous afterdischarge upon brief stimulation of an afferent pathway. After this afterdischarge the cells become refractory to further synaptic stimulation. We find that synchrony, afterdischarge, and prolonged refractoriness are properties that can be expressed in the isolated asomatic neurites of the bag cells. We have distinguished two independent types of refractoriness. The first (type I) is seen as a failure of action potentials generated in the tips of bag cell neurites to invade cell somata. The second form of refractoriness (type II) controls the duration of afterdischarge such that stimuli after the first afterdischarge produce only very short afterdischarges or fail to elicit an afterdischarge. Type II refractoriness is sensitive to serotonin and certain of its analogues, and to dopamine and the methylxanthine phosphodiesterase inhibitors. Extracellularly applied serotonin suppresses an ongoing afterdischarge while dopamine and the phosphodiesterase inhibitors, when applied at the end of the first afterdischarge, generate a subsequent afterdischarge of long duration without further electrical stimulation. None of these compounds influenced the degree of type I refractoriness. We have shown that both serotonin and dopamine stimulate the formation of cyclic AMP in the bag cell clusters and in the pleurovisceral connectives and that the occurrence of an afterdischarge is associated with a specific increase in total cyclic AMP in bag cell bodies. Moreover, afterdischarges can be generated in unstimulated preparations by extracellular application of the cyclic AMP analogues, 8-benzylthio-cyclic AMP or 8-methylthio-cyclic AMP. Our data suggest that serotonin and/or dopamine may control bag cell activity and that activation of adenylate cyclase is linked to bag cell afterdischarge.