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Differential cAMP signaling at hippocampal output synapses.

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.
AuthorsChristian Wozny, Nikolaus Maier, Pawel Fidzinski, Jörg Breustedt, Joachim Behr, Dietmar Schmitz
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 28 Issue 53 Pg. 14358-62 (Dec 31 2008) ISSN: 1529-2401 [Electronic] United States
PMID19118168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Isoquinolines
  • Oligopeptides
  • Protein Kinase Inhibitors
  • Pyridazines
  • Quinoxalines
  • Sulfonamides
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • gamma-glutamyl-glycyl-glycine
  • 8-chloroadenosine-3',5'-cyclic monophosphorothioate
  • Colforsin
  • gabazine
  • Cyclic AMP
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Calcium
Topics
  • Action Potentials (drug effects, physiology)
  • Analysis of Variance
  • Animals
  • Calcium (metabolism)
  • Colforsin (pharmacology)
  • Cyclic AMP (analogs & derivatives, pharmacology, physiology)
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Excitatory Postsynaptic Potentials
  • GABA Antagonists (pharmacology)
  • Hippocampus (cytology)
  • In Vitro Techniques
  • Isoquinolines (pharmacology)
  • Neurons (drug effects, physiology)
  • Oligopeptides (pharmacology)
  • Patch-Clamp Techniques
  • Protein Kinase Inhibitors (pharmacology)
  • Pyridazines (pharmacology)
  • Quinoxalines (pharmacology)
  • Rats
  • Signal Transduction (drug effects, physiology)
  • Sulfonamides (pharmacology)
  • Synapses (drug effects, physiology)
  • Time Factors

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