Regulating anxiety with extrasynaptic inhibition

Botta, Paolo, Demmou, Lynda, Kasugai, Yu, Markovic, Milica, Xu, Chun, Fadok, Jonathan P., Lu, Tingjia, Poe, Michael M., Xu, Li, Cook, James M., Rudolph, Uwe, Sah, Pankaj, Ferraguti, Francesco and Luthi, Andreas (2015) Regulating anxiety with extrasynaptic inhibition. Nature Neuroscience, 18 10: 1493-1500. doi:10.1038/nn.4102

Author Botta, Paolo
Demmou, Lynda
Kasugai, Yu
Markovic, Milica
Xu, Chun
Fadok, Jonathan P.
Lu, Tingjia
Poe, Michael M.
Xu, Li
Cook, James M.
Rudolph, Uwe
Sah, Pankaj
Ferraguti, Francesco
Luthi, Andreas
Title Regulating anxiety with extrasynaptic inhibition
Journal name Nature Neuroscience   Check publisher's open access policy
ISSN 1546-1726
Publication date 2015-10-05
Year available 2015
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1038/nn.4102
Open Access Status Not Open Access
Volume 18
Issue 10
Start page 1493
End page 1500
Total pages 8
Place of publication New York, United States
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Queensland Brain Institute Publications
Official 2016 Collection
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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