Postsynaptic GABAB receptor signalling enhances LTD in mouse cerebellar Purkinje cells

J Physiol. 2007 Dec 1;585(Pt 2):549-63. doi: 10.1113/jphysiol.2007.141010. Epub 2007 Oct 18.


Long-term depression (LTD) of excitatory transmission at cerebellar parallel fibre-Purkinje cell synapses is a form of synaptic plasticity crucial for cerebellar motor learning. Around the postsynaptic membrane of these synapses, B-type gamma-aminobutyric acid receptor (GABABR), a Gi/o protein-coupled receptor for the inhibitory transmitter GABA is concentrated and closely associated with type-1 metabotropic glutamate receptors (mGluR1) whose signalling is a key factor for inducing LTD. We found that in cultured Purkinje cells, GABABR activation enhanced LTD of a glutamate-evoked current (LTDglu), increasing the magnitude of depression. It has been reported that parallel fibre-Purkinje cell synapses receive a micromolar level of GABA spilled over from the synaptic terminals of the neighbouring GABAergic interneurons. This level of GABA was able to enhance LTDglu. Our pharmacological analyses revealed that the betagamma subunits but not the alpha subunit of Gi/o protein mediated GABABR-mediated LTDglu enhancement. Gi/o protein activation was sufficient to enhance LTDglu. In this respect, LTDglu enhancement is clearly distinguished from the previously reported GABABR-mediated augmentation of an mGluR1-coupled slow excitatory postsynaptic potential. Baclofen application for only the induction period of LTDglu was sufficient to enhance LTDglu, suggesting that GABABR signalling may modulate mechanisms underlying LTDglu induction. Baclofen augmented mGluR1-coupled Ca2+ release from the intracellular stores in a Gi/o protein-dependent manner. Therefore, GABABR-mediated LTDglu enhancement is likely to result from augmentation of mGluR1 signalling. Furthermore, pharmacological inhibition of GABABR reduced the magnitude of LTD at parallel fibre-Purkinje cell synapses in cerebellar slices. These findings demonstrate a novel mechanism that would facilitate cerebellar motor learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Agonists / pharmacology
  • Glutamic Acid / pharmacology
  • Long-Term Synaptic Depression / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Patch-Clamp Techniques
  • Protein Subunits / physiology
  • Purkinje Cells / cytology
  • Purkinje Cells / physiology*
  • Receptors, GABA-B / physiology*
  • Receptors, Metabotropic Glutamate / physiology
  • Signal Transduction / physiology


  • GABA Agonists
  • Protein Subunits
  • Receptors, GABA-B
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Glutamic Acid
  • Baclofen