Identification of cyclic AMP as the response regulator for neurosecretory potentiation: a memory model system.

The neural cell line HT4 serves as a model for memory by exhibiting short- and long-term potentiation of neurotransmitter secretion. Previous studies showed that membrane depolarization elicits secretion and that serotonin and N-methyl-D-aspartate receptors are involved in potentiation of the response. Adrenergic and adenosine receptors, which are coupled to adenylate cyclase, are also found to induce potentiation. In addition, the direct evaluation of cAMP levels by forskolin, or by addition of dibutyryl cAMP, induces potentiation. In these different types of stimuli, it is the level of cAMP that is the common factor allowing prediction of whether potentiation will be observed or not. The cAMP level therefore qualifies as the response regulator for this phenomenon. Repetitive adrenergic receptor stimulation results in short-term potentiation, while repetitive adenosine stimulation results in long-term potentiation. This difference can be explained by assuming that some precursor that determines the cAMP level exceeds a threshold, to produce long-term potentiation. This threshold is exceeded by adenosine stimulation but not by stimulation of the beta-adrenergic receptor.