2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and 8-chloroadenosine-3--5--cyclic-monophosphorothioate

cAMP is a critical second messenger involved in synaptic transmission and synaptic plasticity. Here, we show that activation of the adenylyl cyclase by forskolin and application of the cAMP-analog Sp-5,6-DCl-cBIMPS both mimicked and occluded tetanus-induced long-term potentiation (LTP) in subicular bursting neurons, but not in subicular regular firing cells. Furthermore, LTP in bursting cells was inhibited by protein kinase A (PKA) inhibitors Rp-8-CPT-cAMP and H-89. Variations in the degree of EPSC blockade by the low-affinity competitive AMPA receptor-antagonist gamma-d-glutamyl-glycine (gamma-DGG), analysis of the coefficient of variance as well as changes in short-term potentiation suggest an increase of glutamate concentration in the synaptic cleft after expression of LTP. We conclude that presynaptic LTP in bursting cells requires activation of PKA by a calcium-dependent adenylyl cyclase while LTP in regular firing cells is independent of elevated cAMP levels. Our results provide evidence for a differential role of cAMP in LTP at hippocampal output synapses.

Topics: Action Potentials; Analysis of Variance; Animals; Calcium; Colforsin; Cyclic AMP; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA Antagonists; Hippocampus; In Vitro Techniques; Isoquinolines; Neurons; Oligopeptides; Patch-Clamp Techniques; Protein Kinase Inhibitors; Pyridazines; Quinoxalines; Rats; Signal Transduction; Sulfonamides; Synapses; Time Factors