GABA uptake regulates cortical excitability via cell type-specific tonic inhibition

Nat Neurosci. 2003 May;6(5):484-90. doi: 10.1038/nn1043.


GABA(A) receptors can mediate both 'phasic' synaptic inhibition and a persistent 'tonic' form of signaling. We show that, in the presence of intact GABA uptake, guinea pig hippocampal interneurons, but not pyramidal cells, express a tonic GABA(A) receptor-mediated conductance. This conductance was pharmacologically distinct from spontaneous inhibitory postsynaptic currents (IPSCs). Inhibiting GABA uptake resulted in the expression of a comparable GABA(A) receptor-mediated tonic conductance in pyramidal cells. Reducing the tonic conductance in interneurons enhanced their excitability and the inhibitory drive to pyramidal cells. These results point to a role for cell type-dependent tonic inhibition in regulating cortical excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GABA Antagonists / metabolism
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Guinea Pigs
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Interneurons / drug effects
  • Interneurons / metabolism*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Receptors, GABA-A / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / physiology


  • GABA Antagonists
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid