title: Regulating anxiety with extrasynaptic inhibition.
abstract: Aversive experiences can lead to complex behavioral adaptations including increased levels of anxiety and fear generalization. The neuronal mechanisms underlying such maladaptive behavioral changes, however, are poorly understood. Here, using a combination of behavioral, physiological and optogenetic approaches in mouse, we identify a specific subpopulation of central amygdala neurons expressing protein kinase C δ (PKCδ) as key elements of the neuronal circuitry controlling anxiety. Moreover, we show that aversive experiences induce anxiety and fear generalization by regulating the activity of PKCδ(+) neurons via extrasynaptic inhibition mediated by α5 subunit-containing GABAA receptors. Our findings reveal that the neuronal circuits that mediate fear and anxiety overlap at the level of defined subpopulations of central amygdala neurons and demonstrate that persistent changes in the excitability of a single cell type can orchestrate complex behavioral changes.
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors: Paolo
authors: P
authors: Botta
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors: Lynda
authors: L
authors: Demmou
authors: Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Yu
authors: Y
authors: Kasugai
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors: Milica
authors: M
authors: Markovic
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors: Chun
authors: C
authors: Xu
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors: Jonathan P
authors: JP
authors: Fadok
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors: Tingjia
authors: T
authors: Lu
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
authors: Michael M
authors: MM
authors: Poe
authors: Queensland Brain Institute, University of Queensland, St. Lucia, Queensland, Australia.
authors: Li
authors: L
authors: Xu
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
authors: James M
authors: JM
authors: Cook
authors: Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA.
authors: Uwe
authors: U
authors: Rudolph
authors: Queensland Brain Institute, University of Queensland, St. Lucia, Queensland, Australia.
authors: Pankaj
authors: P
authors: Sah
authors: Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Francesco
authors: F
authors: Ferraguti
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors: Andreas
authors: A
authors: Lüthi
mesh_terms: D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D051745:Protein Kinase C-delta / Q000096:biosynthesis; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology
chemical_list: D051745:Protein Kinase C-delta