Neurosteroids increase tonic GABAergic inhibition in the lateral section of the central amygdala in mice

J Neurophysiol. 2015 May 1;113(9):3421-31. doi: 10.1152/jn.00045.2015. Epub 2015 Mar 18.

Abstract

Neurosteroids are formed de novo in the brain and can modulate both inhibitory and excitatory neurotransmission. Recent evidence suggests that the anxiolytic effects of neurosteroids are mediated by the amygdala, a key structure for emotional and cognitive behaviors. Tonic inhibitory signaling via extrasynaptic type A γ-aminobutyric acid receptors (GABA(A)Rs) is known to be crucially involved in regulating network activity in various brain regions including subdivisions of the amygdala. Here we provide evidence for the existence of tonic GABAergic inhibition generated by the activation of δ-subunit-containing GABA(A)Rs in neurons of the lateral section of the mouse central amygdala (CeAl). Furthermore, we show that neurosteroids play an important role in the modulation of tonic GABAergic inhibition in the CeAl. Taken together, these findings provide new mechanistic insights into the effects of pharmacologically relevant neurosteroids in the amygdala and might be extrapolated to the regulation of anxiety.

Keywords: anxiety; central amygdala; extrasynaptic GABAA receptors; neurosteroids; tonic inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysics
  • Central Amygdaloid Nucleus / cytology*
  • Central Amygdaloid Nucleus / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Agents / pharmacology
  • GABAergic Neurons / drug effects*
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Neural Inhibition / drug effects*
  • Neurotransmitter Agents / pharmacology*
  • Patch-Clamp Techniques
  • Quinoxalines / pharmacology
  • Receptors, GABA-A / metabolism

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Agents
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Neurotransmitter Agents
  • Quinoxalines
  • Receptors, GABA-A
  • FG 9041