Requirement of a critical period of GABAergic receptor blockade for induction of a cAMP-mediated long-term depression at CA3-CA1 synapses.
Previous reports show that bath application of the adenosine 3' : 5'-cyclic monophosphate (cAMP) analog, Sp-cAMPS, induces a protein kinase A (PKA)-dependent and protein synthesis-dependent long-term potentiation (LTP) at hippocampal CA3-CA1 synapses. Recently, we reported a novel form of long-term depression (LTD) induced by concurrent application of Sp-cAMPS and picrotoxin, the gamma-aminobutyric acid type A (GABA(A)) receptor antagonist. In the present study, we further investigated the mechanisms underlying such cAMP-mediated LTD. Synaptically connected CA3 and CA1 cells of hippocampal slice cultures were impaled by sharp electrodes. Excitatory postsynaptic potentials recorded from a CA1 pyramidal cell were evoked by single action potentials in a CA3 cell. Picrotoxin was applied to slices at various time points after Sp-cAMPS was perfused. We found that Sp-cAMPS-induced potentiation could be converted to depression when picrotoxin was applied within 30 min after perfusion of Sp-cAMPS. Picrotoxin applied 1 h after perfusion of Sp-cAMPS had no effect on Sp-cAMPS-induced synaptic potentiation. Once LTP was induced by Sp-cAMPS and expressed for 1 h, the subsequent application of Sp-cAMPS and picrotoxin produced no new changes in synaptic strength. Also, once LTD was induced and expressed for 1 h, subsequent Sp-cAMPS produced no new changes in synaptic strength. These findings suggest that a synapse is committed irreversibly to cAMP-mediated LTP or LTD during a critical period and that later signals cannot interconvert these two fates.
Yu
Tzu-Ping
TP
Division of Biology, 1200 E. California Blvd., California Institute of Technology, Pasadena, California 91125, USA.
Lester
Henry A
HA
Davidson
Norman
N
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D000697:Central Nervous System Stimulants; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin