Developmental changes in retrograde messengers involved in depolarization-induced suppression of excitation at parallel fiber-Purkinje cell synapses in rodents

J Neurophysiol. 2007 Jan;97(1):824-36. doi: 10.1152/jn.00735.2006. Epub 2006 Nov 15.

Abstract

At parallel fiber (PF) to Purkinje cell (PC) synapses, depolarization-induced suppression of excitation (DSE) and suppression of PF-excitatory postsynaptic currents (EPSCs) by activation of postsynaptic mGluR1 glutamate (Glu) receptors involve retrograde release of endocannabinoids. However, Levenes et al. suggested instead that Glu was the retrograde messenger in this latter case. Because the study by Levenes et al. was performed in nearly mature rats, whereas most others were performed in juvenile animals, DSE was re-investigated in juvenile versus nearly mature rats and mice. Indeed, DSE was preferred here to agonist-induced suppression of PF-EPSCs, to avoid possible indirect effects in this latter case. In 10- to 12-day-old rats, DSE of PF-EPSCs was entirely mediated through retrograde release of endocannabinoids. In 18- to 22-day-old-rats, DSE was partly resistant to CB1 cannabinoid receptor antagonists. The remaining component was potentiated by the Glu uptake inhibitor d-threo-beta-benzyloxyaspartate (d-TBOA) and blocked by the desensitizing kainate (KA) receptor agonist (2S,4R)-4-methylglutamic acid (SYM 2081). This SYM-2081-sensitive component of DSE was accompanied by a paired-pulse facilitation increase that was also potentiated by d-TBOA and blocked by SYM 2081. In nearly mature wild-type and GluR6 -/- mice, results fully confirmed the presence of an endocannabinoid-independent component of DSE that involves retrograde release of Glu and activation of presynaptic KA receptors including GluR6 receptor subunits. Therefore retrograde release of Glu by PCs participates to DSE at PF-PC synapses in nearly mature rodents but not in juvenile ones, and Glu probably operates through activation of presynaptic KA receptors that include GluR6 receptor subunits.

MeSH terms

  • Animals
  • Animals, Newborn
  • Aspartic Acid / pharmacology
  • Cannabinoid Receptor Modulators / metabolism*
  • Cell Differentiation / physiology
  • Cell Membrane / metabolism
  • Cerebellar Cortex / cytology
  • Cerebellar Cortex / growth & development*
  • Cerebellar Cortex / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • GluK2 Kainate Receptor
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Inhibition / physiology*
  • Organ Culture Techniques
  • Purkinje Cells / cytology
  • Purkinje Cells / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, Kainic Acid / genetics*
  • Second Messenger Systems / drug effects
  • Second Messenger Systems / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Cannabinoid Receptor Modulators
  • Excitatory Amino Acid Agonists
  • Receptor, Cannabinoid, CB1
  • Receptors, Kainic Acid
  • benzyloxyaspartate
  • Aspartic Acid
  • Glutamic Acid