Summary
Using an in vitro slice preparation, we studied the effects, on parallel fiber (PF)-mediated EPSPs, of coactivation of metabotropic-glutamate receptors and of voltage-gated calcium (Ca) channels of Purkinje cells (PCs) by bath application of 50 μM trans-1-aminocyclopentyl-1,3-dicarboxylate (trans-ACPD) and by direct depolarization of the cells, respectively. These effects were compared with changes in synaptic efficacy obtained when α-amino-3hydroxy-5-methylisoxalone-4-propionate (AMPA) receptors of PCs were also activated through stimulation of PFs during the pairing protocol, as well as when similar experiments were performed without trans-ACPD in the bath. In a control medium, pairing for 1 min of PF-mediated EPSPs evoked at 1 Hz with Ca spikes evoked by steady depolarization of PCs (n = 13) led to LTD of synaptic transmission in 9 cases whereas for the others EPSPs were not affected. No LTD occurred in 9 out of 10 other cells tested when PF stimulation was omitted during the 1 min period of Ca spike firing of PCs. Bath application of 50 μM trans-ACPD, in conjunction with the same pairing protocol as before (n = 8), led to a significantly larger LTD of PF-mediated EPSPs after washing out of this drug. Moreover, a clearcut LTD of PF-mediated EPSPs was also observed in 5 of the 8 other cells, when PF stimulation was omitted during Ca spike firing in the presence of trans-ACPD. As trans-ACPD alone induced fully reversible depressions of EPSPs, coactivation of metabotropic-glutamate receptors and of voltage-gated Ca channels is therefore likely to be sufficient to induce LTD of PF-mediated EPSPs.
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References
Albus JS (1971) A theory of cerebellar function. Math Biosci 10: 25–61
Bezprozvanny I, Watras J, Ehrlich BE (1991) Bell-shaped calcium response curves of Ins(1,4,5)P3- and calcium gated channels from endoplasmic reticulum of cerebellum. Nature 351: 751–754
Blackstone CD, Supattapone S, Snyder SH (1989) Inositolphospholipid-linked glutamate receptors mediate cerebellar parallel-fiber-Purkinje-cell synaptic transmission. Proc Natl Acad Sci USA 86: 4316–4320
Crepel F, Jaillard D (1990) Protein kinases, nitric oxide and long-term depression of synapses in the cerebellum. Neuroreport 1: 133–136
Crepel F, Jaillard D (1991) Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy. An in vitro study. J Physiol (Lond) 432: 123–141
Crepel F, Krupa M (1988) Activation of protein kinase C decreases glutamate sensitivity of cerebellar Purkinje cells. Brain Res 458: 397–401
Crepel F, Krupa M (1990) Modulation of the responsiveness of cerebellar Purkinje cells to excitatory amino acids. In: Y. Ben Ari (eds) Excitatory amino acids and neuronal plasticity. Plenum Press, New York, pp 323–329
Crepel F, Daniel H, Hemart N, Jaillard D (1991) Effects of ACPD and AP3 on parallel-fibre-mediated EPSPs of Purkinje cells in cerebellar slices in vitro. Exp Brain Res 86: 402–406
Hirano T (1990) Effects of postsynaptic depolarization in the induction of synaptic depression between a granule cell and a Purkinje cell in rat cerebellar culture. Neurosci Lett 119: 145–147
Ito M (1989) Long term depression. Ann Rev Neurosci 12: 85–102
Ito M, Karachot L (1990) Messengers mediating long-term desensitization in cerebellar Purkinje cells. Neuroreport 1: 129–132
Kano M, Kato M (1987) Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Nature 325: 276–279
Knöpfel T, Vranesic I, Staub C (1991a) Response to metabotropic glutamate receptor activation in cerebellar Purkinje cells. Soc Neurosci Abst (USA) 17: 336
Knöpfel T, Vranesic I, Staub C, Gähwiler B (1991b) Climbing fibre responses in olivo-cerebellar slice cultures. II. Dynamics of cytosolic calcium in Purkinje cells. Eur J Neurosci 3: 343–348
Konnerth A, Dreessen J, Augustine GJ (1990) Intracellular calcium triggers long-term depression in the cerebellum. Pflügers Archiv 415 [Suppl 1]:R 84
Linden DJ, Connor JA (1991) Participation of postsynaptic PKC in cerebellar long-term depression in culture. Science 254: 1656–1659
Linden DJ, Dickinson MH, Smeyne M, Connor JA (1991) A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron 7: 81–89
Lohmann SM, Walter U, Miller PE, Greengard P, Camilli PD (1981) Immunohistochemical localization of cyclic GMP-dependent protein kinase in mammalian brain. Proc Natl Acad Sci USA 78: 653–657
Lovinger DM (1991) Trans-ACPD decreases synaptic excitation in rat striatal slices through a presynaptic action. Neurosci Lett 129: 17–21
Palmer E, Monaghan DT, Cotman CW (1989) Trans-ACPD, a selective agonist of the phosphoinositide-coupled excitatory amino acid receptors. Eur J Pharmacol 166: 585–587
Ross W, Werman R (1987) Mapping calcium transients in the dendrites of Purkinje cells from the guinea-pig cerebellum in vitro. J Physiol (Lond) 389: 319–336
Sakurai M (1990) Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression. Proc Natl Acad Sci USA 87: 8383–8385
Sladeczek F, Pin JP, Recasens M, Bockaert J, Weiss S (1985) Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 314: 717–719
Sugiyama H, Ito I, Hirono C (1987) A new type of glutamate receptor linked to inositol phospholipid metabolism. Nature 325: 531–533
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Daniel, H., Hemart, N., Jaillard, D. et al. Coactivation of metabotropic glutamate receptors and of voltage-gated calcium channels induces long-term depression in cerebellar Purkinje cells in vitro. Exp Brain Res 90, 327–331 (1992). https://doi.org/10.1007/BF00227245
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DOI: https://doi.org/10.1007/BF00227245