Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Neuropsychopharmacology. 2016 Jul;41(8):2011-23. doi: 10.1038/npp.2015.371. Epub 2016 Jan 4.

Abstract

Anxiety disorders are debilitating psychiatric illnesses with detrimental effects on human health. These heightened states of arousal are often in the absence of obvious threatening cues and are difficult to treat owing to a lack of understanding of the neural circuitry and cellular machinery mediating these conditions. Activation of noradrenergic circuitry in the basolateral amygdala is thought to have a role in stress, fear, and anxiety, and the specific cell and receptor types responsible is an active area of investigation. Here we take advantage of two novel cellular approaches to dissect the contributions of G-protein signaling in acute and social anxiety-like states. We used a chemogenetic approach utilizing the Gαs DREADD (rM3Ds) receptor and show that selective activation of generic Gαs signaling is sufficient to induce acute and social anxiety-like behavioral states in mice. Second, we use a recently characterized chimeric receptor composed of rhodopsin and the β2-adrenergic receptor (Opto-β2AR) with in vivo optogenetic techniques to selectively activate Gαs β-adrenergic signaling exclusively within excitatory neurons of the basolateral amygdala. We found that optogenetic induction of β-adrenergic signaling in the basolateral amygdala is sufficient to induce acute and social anxiety-like behavior. These findings support the conclusion that activation of Gαs signaling in the basolateral amygdala has a role in anxiety. These data also suggest that acute and social anxiety-like states may be mediated through signaling pathways identical to β-adrenergic receptors, thus providing support that inhibition of this system may be an effective anxiolytic therapy.

Publication types

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

MeSH terms

  • Animals
  • Anxiety / metabolism*
  • Basolateral Nuclear Complex / metabolism*
  • Behavior, Animal
  • GTP-Binding Protein alpha Subunits / metabolism*
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Optogenetics
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Signal Transduction
  • Social Behavior

Substances

  • GTP-Binding Protein alpha Subunits
  • Receptors, Adrenergic, beta-2