Journal of Neurophysiology, Vol 68, Issue 4 1453-1462, Copyright © 1992 by APS

ARTICLES

Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse

S. R. Glaum, N. T. Slater, D. J. Rossi and R. J. Miller
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.

1. The role of metabotropic glutamate receptors at the parallel fiber (PF)-Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				F. Ferraguti, L. Crepaldi, and F. Nicoletti Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives Pharmacol. Rev., December 1, 2008; 60(4): 536 - 581. [Abstract] [Full Text] [PDF]

				M. Hamann, D. J. Rossi, C. Mohr, A. L. Andrade, and D. Attwell The electrical response of cerebellar Purkinje neurons to simulated ischaemia Brain, October 1, 2005; 128(10): 2408 - 2420. [Abstract] [Full Text] [PDF]

				R. Bertram, J. Swanson, M. Yousef, Z.-P. Feng, and G. W. Zamponi A Minimal Model for G Protein-Mediated Synaptic Facilitation and Depression J Neurophysiol, September 1, 2003; 90(3): 1643 - 1653. [Abstract] [Full Text] [PDF]

				N. H. Barmack and V. Yakhnitsa Cerebellar Climbing Fibers Modulate Simple Spikes in Purkinje Cells J. Neurosci., August 27, 2003; 23(21): 7904 - 7916. [Abstract] [Full Text] [PDF]

				C. Levenes, H. Daniel, and F. Crepel Retrograde modulation of transmitter release by postsynaptic subtype 1 metabotropic glutamate receptors in the rat cerebellum J. Physiol., November 15, 2001; 537(1): 125 - 140. [Abstract] [Full Text] [PDF]

				P. Calabresi, P. Gubellini, D. Centonze, G. Sancesario, M. Morello, M. Giorgi, A. Pisani, and G. Bernardi A Critical Role of the Nitric Oxide/cGMP Pathway in Corticostriatal Long-Term Depression J. Neurosci., April 1, 1999; 19(7): 2489 - 2499. [Abstract] [Full Text] [PDF]

				C. A. Del Negro and S. H. Chandler Regulation of Intrinsic and Synaptic Properties of Neonatal Rat Trigeminal Motoneurons by Metabotropic Glutamate Receptors J. Neurosci., November 15, 1998; 18(22): 9216 - 9226. [Abstract] [Full Text] [PDF]

				Z. Chu and J. J. Hablitz Activation of Group I mGluRs Increases Spontaneous IPSC Frequency in Rat Frontal Cortex J Neurophysiol, August 1, 1998; 80(2): 621 - 627. [Abstract] [Full Text] [PDF]

				B. A. McCool, J.-P. Pin, M. M. Harpold, P. F. Brust, K. A. Stauderman, and D. M. Lovinger Rat group I Metabotropic Glutamate Receptors Inhibit Neuronal Ca2+ Channels via Multiple Signal Transduction Pathways in HEK 293 Cells J Neurophysiol, January 1, 1998; 79(1): 379 - 391. [Abstract] [Full Text] [PDF]

				J. G. Netzeband, K. L. Parsons, D. D. Sweeney, and D. L. Gruol Metabotropic Glutamate Receptor Agonists Alter Neuronal Excitability and Ca2+ Levels via the Phospholipase C Transduction Pathway in Cultured Purkinje Neurons J Neurophysiol, July 1, 1997; 78(1): 63 - 75. [Abstract] [Full Text] [PDF]

				S. C. Molitor and P. B. Manis Evidence for Functional Metabotropic Glutamate Receptors in the Dorsal Cochlear Nucleus J Neurophysiol, April 1, 1997; 77(4): 1889 - 1905. [Abstract] [Full Text] [PDF]

				K Nakazawa, S Mikawa, and M Ito Persistent phosphorylation parallels long-term desensitization of cerebellar purkinje cell AMPA-type glutamate receptors. Learn. Mem., January 1, 1997; 3(6): 578 - 591. [Abstract] [PDF]

				R. Pekhletski, R. Gerlai, L. S. Overstreet, X.-P. Huang, N. Agopyan, N. T. Slater, W. Abramow-Newerly, J. C. Roder, and D. R. Hampson Impaired Cerebellar Synaptic Plasticity and Motor Performance in Mice Lacking the mGluR4 Subtype of Metabotropic Glutamate Receptor J. Neurosci., October 15, 1996; 16(20): 6364 - 6373. [Abstract] [Full Text] [PDF]

				X.-W. Dong, D. Morin, and J. L. Feldman Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons J. Neurosci., August 15, 1996; 16(16): 4971 - 4982. [Abstract] [Full Text] [PDF]

				J. C. Fiala, S. Grossberg, and D. Bullock Metabotropic Glutamate Receptor Activation in Cerebellar Purkinje Cells as Substrate for Adaptive Timing of the Classically Conditioned Eye-Blink Response J. Neurosci., June 1, 1996; 16(11): 3760 - 3774. [Abstract] [Full Text] [PDF]