Regulating anxiety with extrasynaptic inhibition.
- Botta P Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Demmou L Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Kasugai Y Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
- Markovic M Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Xu C Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Fadok JP Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Lu T Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Poe MM Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
- Xu L Queensland Brain Institute, University of Queensland, St. Lucia, Queensland, Australia.
- Cook JM Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
- Rudolph U Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA.
- Sah P Queensland Brain Institute, University of Queensland, St. Lucia, Queensland, Australia.
- Ferraguti F Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
- Lüthi A Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- 2015-09-01
Published in:
- Nature neuroscience. - 2015
Amygdala
Animals
Anxiety
Conditioning, Classical
Disease Models, Animal
Gene Knockdown Techniques
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Neural Inhibition
Neurons
Optogenetics
Patch-Clamp Techniques
Protein Kinase C-delta
Stress, Psychological
English
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1038/nn.4102
- PMID 26322928
- Persistent URL
- https://sonar.ch/global/documents/90538
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