Phasic, nonsynaptic GABA-A receptor-mediated inhibition entrains thalamocortical oscillations

J Neurosci. 2014 May 21;34(21):7137-47. doi: 10.1523/JNEUROSCI.4386-13.2014.

Abstract

GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs. In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically during burst firing of nRT cells and provide sufficient GABA-AR activation to control major thalamocortical oscillations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / physiology*
  • Dependovirus / genetics
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / physiology*
  • Neurons / physiology*
  • Pyridazines / pharmacology
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Synapses / drug effects
  • Synapses / genetics
  • Thalamus / physiology*
  • Vesicular Glutamate Transport Protein 2 / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Pyridazines
  • Receptors, GABA-A
  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • gamma-Aminobutyric Acid
  • gabazine