Modulation of stimulus-specific adaptation by GABA(A) receptor activation or blockade in the medial geniculate body of the anaesthetized rat

J Physiol. 2014 Feb 15;592(4):729-43. doi: 10.1113/jphysiol.2013.261941. Epub 2013 Oct 7.

Abstract

Stimulus-specific adaptation (SSA), which describes adaptation to repeated sounds concurrent with the maintenance of responsiveness to uncommon ones, may be an important neuronal mechanism for the detection of and attendance to rare stimuli or for the detection of deviance. It is well known that GABAergic neurotransmission regulates several different response properties in central auditory system neurons and that GABA is the major inhibitory neurotransmitter acting in the medial geniculate body (MGB). The mechanisms underlying SSA are still poorly understood; therefore, the primary aim of the present study was to examine what role, if any, MGB GABAergic circuits play in the generation and/or modulation of SSA. Microiontophoretic activation of GABA(A) receptors (GABA(A)Rs) with GABA or with the selective GABA(A)R agonist gaboxadol significantly increased SSA (computed with the common SSA index, CSI) by decreasing responses to common stimuli while having a lesser effect on responses to novel stimuli. In contrast, GABA(A)R blockade using gabazine resulted in a significant decrease in SSA. In all cases, decreases in the CSI during gabazine application were accompanied by an increase in firing rate to the stimulus paradigm. The present findings, in conjunction with those of previous studies, suggest that GABA(A)-mediated inhibition does not generate the SSA response, but can regulate the level of SSA sensitivity in a gain control manner. The existence of successive hierarchical levels of processing through the auditory system suggests that the GABAergic circuits act to enhance mechanisms to reduce redundant information.

Publication types

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

MeSH terms

  • Acoustic Stimulation
  • Adaptation, Physiological*
  • Anesthesia, General
  • Animals
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Agonists / pharmacology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology
  • Geniculate Bodies / cytology
  • Geniculate Bodies / metabolism
  • Geniculate Bodies / physiology*
  • Isoxazoles / pharmacology
  • Male
  • Pyridazines / pharmacology
  • Rats
  • Rats, Inbred F344
  • Receptors, GABA-A / metabolism*

Substances

  • GABA Antagonists
  • GABA-A Receptor Agonists
  • Isoxazoles
  • Pyridazines
  • Receptors, GABA-A
  • gabazine
  • gaboxadol