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Regulating anxiety with extrasynaptic inhibition

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 optogeneti...

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Detalles Bibliográficos
Autores principales: 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, Lüthi, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607767/
https://www.ncbi.nlm.nih.gov/pubmed/26322928
http://dx.doi.org/10.1038/nn.4102
Descripción
Sumario: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 α(5) subunit-containing GABA(A) 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.