Regulating anxiety with extrasynaptic inhibition

Nature Neuroscience
Paolo BottaAndreas Lüthi

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.

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Citations

Apr 28, 2016·Molecular Pharmaceutics·Gloria S ForkuoLeggy A Arnold
Apr 14, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lauren M BehlkeUwe Rudolph
Aug 9, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·A ChagraouiF Thibaut
Jul 15, 2017·PLoS Computational Biology·Laurent MackayAnmar Khadra
Apr 10, 2018·Experimental & Molecular Medicine·Olga BabaevDilja Krueger-Burg
Feb 25, 2017·F1000Research·Hanns Möhler, Uwe Rudolph
Aug 22, 2017·Nature Neuroscience·Amelia M DouglassRüdiger Klein
Nov 6, 2018·The Journal of Pharmacology and Experimental Therapeutics·Yan-Mei LiuFei Li
Apr 20, 2019·Science·Jan GründemannAndreas Lüthi
Sep 4, 2015·Journal of Neurophysiology·Ludmila SosulinaHans-Christian Pape
Jul 19, 2017·Learning & Memory·Wen-Hua ZhangBing-Xing Pan
Aug 18, 2017·Learning & Memory·Travis D Goode, Stephen Maren
Nov 26, 2015·Nature Neuroscience·Paolo BottaAndreas Lüthi
Oct 23, 2019·Nature Neuroscience·Sabine KrabbeAndreas Lüthi
Jun 23, 2018·Science·Eric AugierMarkus Heilig
Apr 16, 2019·Frontiers in Molecular Neuroscience·Nathanael O'Neill, Sergiy Sylantyev
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Jan 1, 2020·Biological Psychiatry·Zheng-Yi LuoTian-Ming Gao
Jan 9, 2021·Translational Psychiatry·Chunmei WangYong Xu

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Methods Mentioned

BETA
electron microscopy
light microscopy
transgenic

Software Mentioned

Clampex
Photoshop
Clampfit
Mini Analysis
Adobe
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SigmaPlot
RNAi Explorer
NeuroExplorer
GraphPad Prism

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