MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors.
Parkinson's disease (PD)-like symptoms and cognitive deficits are inducible by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Since cognitive abilities, including memory formations rely also on hippocampus, we set out to clarify the effects of MPTP on hippocampal physiology. We show that bath-application of MPTP (25 μM) to acute hippocampal slices enhanced AMPA receptor-mediated field excitatory postsynaptic potentials (AMPAr-fEPSPs) transiently, whereas N-methyl-D-aspartate (NMDA) receptor-mediated fEPSPs (NMDAr-fEPSPs) were facilitated persistently. The MPTP-mediated transient AMPAr-fEPSP facilitation was antagonized by the dopamine D2-like receptor antagonists, eticlopride (1 μM) and sulpiride (1 and 40 μM). In contrast, the persistent enhancement of NMDAr-fEPSPs was prevented by the dopamine D1-like receptor antagonist SCH23390 (10 μM). In addition, we show that MPTP decreased paired-pulse facilitation of fEPSPs and mEPSCs frequency. Regarding activity-dependent synaptic plasticity, 25 μM MPTP transformed short-term potentiation (STP) into a long-term potentiation (LTP) and caused a slow onset potentiation of a non-tetanized synaptic input after induction of LTP in a second synaptic input. This heterosynaptic slow onset potentiation required activation of dopamine D1-like and NMDA-receptors. We conclude that acute MPTP application affects basal synaptic transmission by modulation of presynaptic vesicle release and facilitates NMDAr-fEPSPs as well as activity-dependent homo- and heterosynaptic plasticity under participation of dopamine receptors.
Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Guoqi
G
Zhu
Yuying
Y
Huang
Ying
Y
Chen
Yinghan
Y
Zhuang
Thomas
T
Behnisch
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001703:Biophysics; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D011810:Quinoxalines; D011954:Receptors, Dopamine; C534628:SCH 23390; D026941:Sodium Channel Blockers; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin; C056639:2-amino-5-phosphopentanoic acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D013469:Sulpiride; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014633:Valine