title: Time-dependent reversal of long-term potentiation by low-frequency stimulation at the hippocampal mossy fiber-CA3 synapses.
abstract: Using mouse hippocampal slices, we studied the induction of depotentiation of long-term potentiation (LTP) at the mossy fiber synapses onto CA3 pyramidal neurons. A long train of low-frequency (1 Hz/900 pulses) stimulation (LFS) induced a long-term depression of baseline synaptic transmission or depotentiation of previously established LTP, which was reversible and was independent of NMDA receptor activation. This LFS-induced depotentiation was observed when the stimulus was delivered 1 or 10 min after LTP induction. However, when LFS was applied at 30 min after induction, significantly less depotentiation was found. The induction of depotentiation on one input was associated with a heterosynaptic reverse of the LTP induced previously on a separate pathway. In addition, this LFS-induced depotentiation appeared to be mediated by the activation of group 2 metabotropic glutamate receptors (mGluRs), because it was mimicked by the bath-applied group 2 agonist (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl) glycine and was specifically inhibited by the group 2 antagonists (S)-alpha-methyl-4-carboxyphenylglycine and (alphaS)-alpha-amino-alpha-(1S,2S)-2-carboxycyclopropyl-9H-xanthine-9-propanic acid. Moreover, the induction of depotentiation was entirely normal when synaptic transmission is blocked by glutamate receptor antagonist kynurenic acid and was associated with a reversal of paired-pulse facilitation attenuation during LTP expression. Pretreatment of the hippocampal slices with G(i/o)-protein inhibitor pertussis toxin (PTX) prevented the LFS-induced depotentiation. These results suggest that the activation of presynaptic group 2 mGluRs and in turn triggering a PTX-sensitive G(i/o)-protein-coupled signaling cascade may contribute to the LFS-induced depotentiation at the mossy fiber-CA3 synapses.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City 701, Taiwan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: K S
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007736:Kynurenic Acid