Differential cAMP signaling at hippocampal output synapses.
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.
Wozny
Christian
C
Neuroscience Research Center, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. cwozny@mrc-lmb.cam.ac.uk
Maier
Nikolaus
N
Fidzinski
Pawel
P
Breustedt
Jörg
J
Behr
Joachim
J
Schmitz
Dietmar
D
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007546:Isoquinolines; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D011810:Quinoxalines; D013449:Sulfonamides; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C048439:gamma-glutamyl-glycyl-glycine; C074155:8-chloroadenosine-3',5'-cyclic monophosphorothioate; D005576:Colforsin; C049853:gabazine; D000242:Cyclic AMP; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium