Potentiation of mossy fiber-evoked EPSPs in turtle cerebellar Purkinje cells by the metabotropic glutamate receptor agonist 1S,3R-ACPD.
1. The effects of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD on excitatory postsynaptic potentials (EPSPs) evoked by stimulation of mossy fibers (MF) and parallel fibers (PF) were examined in turtle cerebellar Purkinje cells. 2. 1S,3R-ACPD (1-25 microM) reversibly potentiated the amplitude of the MF-evoked EPSPs and revealed a late, slow EPSP component, but was without effect on PF-evoked EPSPs. The potentiation of both components of MF-evoked EPSPs was dose dependent, with an ED50 of approximately 3 microM. At higher doses (15-25 microM) 1S,3R-ACPD produced a direct depolarization of Purkinje cells in 57% of cells examined. 3. The enhancement of MF EPSPs by 1S,3R-ACPD was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (AP-5), but not by the mGluR antagonist L-2-amino-3-phosphonopionic acid (L-AP3; 1 mM), or the 1R,3S isomer of ACPD (25-500 microM). 4. The results demonstrate that mGluR activation by 1S,3R-ACPD produces a potent, stereospecific facilitation of NMDA receptor-mediated transmission at the MF-granule cell synapse.
Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611.
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects*; D005971:Glutamates / Q000502:physiology; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014426:Turtles
D005971:Glutamates; D009498:Neurotoxins; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015763:2-Amino-5-phosphonovalerate