Coactivation of metabotropic glutamate receptors and of voltage-gated calcium channels induces long-term depression in cerebellar Purkinje cells in vitro

Exp Brain Res. 1992;90(2):327-31. doi: 10.1007/BF00227245.


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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azasteroids / pharmacology
  • Calcium Channels / physiology*
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Evoked Potentials / physiology
  • In Vitro Techniques
  • Ion Channel Gating / physiology*
  • Neuronal Plasticity / drug effects
  • Oxidoreductases / antagonists & inhibitors
  • Pregnanediones / pharmacology
  • Purkinje Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / physiology*
  • Synaptic Transmission / physiology


  • Azasteroids
  • Calcium Channels
  • Pregnanediones
  • Receptors, Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • 4-aza-4-methylpregnane-3,20-dione
  • Oxidoreductases