title: Spike-timing-dependent plasticity at resting and conditioned lateral perforant path synapses on granule cells in the dentate gyrus: different roles of N-methyl-D-aspartate and group I metabotropic glutamate receptors.
abstract: We examined the mechanisms underlying spike-timing-dependent plasticity induction at resting and conditioned lateral perforant pathway (LPP) synapses in the rat dentate gyrus. Two stimulating electrodes were placed in the outer third of the molecular layer and in the granule cell layer in hippocampal slices to evoke field excitatory postsynaptic potentials (fEPSPs) and antidromic field somatic spikes (afSSs), respectively. Long-term potentiation (LTP) of LPP synapses was induced by paired stimulation with fEPSP preceding afSS. Reversal of the temporal order of fEPSP and afSS stimulation resulted in long-term depression (LTD). Induction of LTP or LTD was blocked by D,L-2-amino-5-phosphonopentanoic acid (AP5), showing that both effects were N-methyl-D-aspartate receptor (NMDAR)-dependent. Induction of LTP was also blocked by inhibitors of calcium-calmodulin kinase II, protein kinase C or mitogen-activated/extracellular-signal regulated kinase, suggesting that these are downstream effectors of NMDAR activation, whereas induction of LTD was blocked by inhibitors of protein kinase C and protein phosphatase 2B. At LPP synapses previously potentiated by high-frequency stimulation or depressed by low-frequency stimulation, paired fEPSP-afSS stimulation resulted in 'de-depression' at depressed LPP synapses but had no effect on potentiated synapses, whereas reversal of the temporal order of fEPSP-afSS stimulation resulted in 'de-potentiation' at potentiated synapses but had no effect on depressed synapses. Induction of de-depression and de-potentiation was unaffected by ap5 but was blocked by 2-methyl-6-(phenylethynyl) pyridine hydrochloride, a group I metabotropic glutamate receptor blocker, showing that both were NMDAR-independent but group I metabotropic glutamate receptor-dependent. In conclusion, our results show that spike-timing-dependent plasticity can occur at both resting and conditioned LPP synapses, its induction in the former case being NMDAR-dependent and, in the latter, group I metabotropic glutamate receptor-dependent.
authors.affiliation: Department of Life Science, College of Life Science, National Taiwan University, 1 Sec.4 Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
authors.forename: Hsiu-Wen
authors.initials: HW
authors.lastname: Yang
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Wang
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Gong
authors.forename: Tsai-Hsien
authors.initials: TH
authors.lastname: Chiu
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Min
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018891:Dentate Gyrus / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019580:Perforant Pathway / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D011810:Quinoxalines; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; C056723:FG 9041