Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Analysis of Variance
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Animals
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Calcium / metabolism
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Colforsin / pharmacology
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP / physiology*
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Electric Stimulation
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials
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GABA Antagonists / pharmacology
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Hippocampus / cytology*
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In Vitro Techniques
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Isoquinolines / pharmacology
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Neurons / drug effects
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Neurons / physiology*
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Oligopeptides / pharmacology
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Patch-Clamp Techniques
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Protein Kinase Inhibitors / pharmacology
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Pyridazines / pharmacology
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Quinoxalines / pharmacology
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Rats
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Sulfonamides / pharmacology
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Synapses / drug effects
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Synapses / physiology*
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Time Factors
Substances
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Isoquinolines
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Oligopeptides
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Protein Kinase Inhibitors
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Pyridazines
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Quinoxalines
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Sulfonamides
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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gamma-glutamyl-glycyl-glycine
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8-chloroadenosine-3',5'-cyclic monophosphorothioate
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Colforsin
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gabazine
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Cyclic AMP
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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Calcium