Coactivation of metabotropic glutamate receptors and of voltage-gated calcium channels induces long-term depression in cerebellar Purkinje cells in vitro.
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 microM trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) and by direct depolarization of the cells, respectively. These effects were compared with changes in synaptic efficacy obtained when alpha-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 microM 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 clear-cut 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Daniel
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H
Laboratoire de Neurobiologie et Neuropharmacologie du Développement, URA CNRS, Université Paris-Sud, Orsay, France.
Hemart
N
N
Jaillard
D
D
Crepel
F
F
D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011277:Pregnanediones / Q000494:pharmacology; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D001378:Azasteroids; D015220:Calcium Channels; D011277:Pregnanediones; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C040124:4-aza-4-methylpregnane-3,20-dione; D010088:Oxidoreductases