Gamma-aminobutyric acid(B) receptor activation suppresses stimulus-evoked burst firing in rat substantia nigra reticulata neurons

Neuroreport. 2012 Jan 4;23(1):40-4. doi: 10.1097/WNR.0b013e32834e4899.

Abstract

Previous whole-cell patch-pipette studies showed that focal electrical stimulation of the subthalamic nucleus (STN) evokes a long-lasting complex excitatory postsynaptic currents (EPSC) and synaptically evoked bursts of action potentials in substantia nigra pars reticulata (SNR) neurons. Although synaptically evoked bursting may play a role in normal physiology, excessive burst firing correlates with symptoms of Parkinson's disease. We used patch-pipette recordings in rat brain slices to study the effects of baclofen on complex EPSCs and STN-induced burst firing in SNR neurons. Baclofen (1 µM) caused a reversible, 73% reduction in complex EPSCs, and this effect was blocked by the γ-aminobutyric acid(B) antagonist CGP35348 (100 µM). Using the loose-patch method to record extracellular potentials, a lower concentration of baclofen (100 nM) inhibited STN-evoked bursts, while leaving spontaneous firing of action potentials less affected. We suggest that strategies that selectively inhibit burst firing in the SNR might have therapeutic potential in the treatment of Parkinson's disease.

Publication types

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

MeSH terms

  • Action Potentials
  • Animals
  • Baclofen / pharmacology
  • Excitatory Postsynaptic Potentials* / drug effects
  • Excitatory Postsynaptic Potentials* / physiology
  • GABA Antagonists / pharmacology
  • GABA-B Receptor Agonists / pharmacology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / physiology
  • Substantia Nigra / cytology
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiology*
  • Synaptic Transmission / drug effects

Substances

  • GABA Antagonists
  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • Baclofen