Activation of presynaptic kainate receptors suppresses GABAergic synaptic transmission in the rat globus pallidus

Neuroscience. 2007 Oct 26;149(2):338-49. doi: 10.1016/j.neuroscience.2007.07.017. Epub 2007 Jul 20.


The globus pallidus (GP) plays a central integrative role in the basal ganglia circuitry. It receives strong GABAergic inputs from the striatum (Str) and significant glutamatergic afferents from the subthalamic nucleus (STN). The change in firing rate and pattern of GP neurons is a cardinal feature of Parkinson's disease pathophysiology. Kainate receptor (KAR) GluR6/7 subunit immunoreactivity is expressed presynaptically in GABAergic striatopallidal terminals which provides a substrate for regulation of GABAergic transmission in GP. To test this hypothesis, we recorded GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) in the GP following electrical stimulation of the Str. Following blockade of AMPA and N-methyl-d-aspartate receptors with selective antagonists, bath application of kainate (KA) (0.3-3 microM) reduced significantly the amplitude of evoked IPSCs. This inhibition was associated with a significant increase in paired-pulse facilitation ratio and a reduction of the frequency, but not amplitude, of miniature inhibitory postsynaptic currents (mIPSCs), suggesting a presynaptic site of KA action. The KA effects on striatopallidal GABAergic transmission were blocked by the G-protein inhibitor, N-ethylmaleimide (NEM), or protein kinase C (PKC) inhibitor calphostin C. Our results demonstrate that KAR activation inhibits GABAergic transmission through a presynaptic G protein-coupled, PKC-dependent metabotropic mechanism in the rat GP. These findings open up the possibility for the development of KA-mediated pharmacotherapies aimed at decreasing the excessive and abnormally regulated inhibition of GP neurons in Parkinson's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Data Interpretation, Statistical
  • Electric Stimulation
  • Electrophysiology
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Globus Pallidus / drug effects*
  • Kainic Acid / pharmacology
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Neostriatum / physiology
  • Patch-Clamp Techniques
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Kinase C / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Kainic Acid / agonists*
  • Receptors, Presynaptic / agonists*
  • Synapses / physiology
  • Synaptic Transmission / drug effects*
  • gamma-Aminobutyric Acid / physiology*


  • Enzyme Inhibitors
  • Receptors, Kainic Acid
  • Receptors, Presynaptic
  • gamma-Aminobutyric Acid
  • Protein Kinase C
  • biocytin
  • Lysine
  • Kainic Acid