title: Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States.
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.
authors.affiliation: Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St Louis, Missouri, USA.|Washington University Pain Center, Washington University School of Medicine, St Louis, Missouri, USA.|Division of Biology and Biomedical Sciences, Washington University School of Medicine, St Louis, Missouri, USA.|Department of Neuroscience, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Siuda
authors.affiliation: Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St Louis, Missouri, USA.|Washington University Pain Center, Washington University School of Medicine, St Louis, Missouri, USA.|Department of Neuroscience, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Ream
authors.initials: R
authors.lastname: Al-Hasani
authors.affiliation: Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St Louis, Missouri, USA.|Washington University Pain Center, Washington University School of Medicine, St Louis, Missouri, USA.|Division of Biology and Biomedical Sciences, Washington University School of Medicine, St Louis, Missouri, USA.|Department of Neuroscience, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Jordan G
authors.identifier: 0000-0001-8295-0664
authors.initials: JG
authors.lastname: McCall
authors.affiliation: Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Dionnet L
authors.initials: DL
authors.lastname: Bhatti
authors.affiliation: Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St Louis, Missouri, USA.|Washington University Pain Center, Washington University School of Medicine, St Louis, Missouri, USA.|Division of Biology and Biomedical Sciences, Washington University School of Medicine, St Louis, Missouri, USA.|Department of Neuroscience, Washington University School of Medicine, St Louis, Missouri, USA.|Department of Biomedical Engineering, Washington University in St. Louis, St Louis, Missouri, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bruchas
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D001522:Behavior, Animal; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D062308:Optogenetics; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction; D012919:Social Behavior
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D018343:Receptors, Adrenergic, beta-2