Regulating anxiety with extrasynaptic inhibition

Paolo Botta, Lynda Demmou, Yu Kasugai, Milica Markovic, Chun Xu, Jonathan P. Fadok, Tingjia Lu, Michael M. Poe, Li Xu, James M. Cook, Uwe Rudolph, Pankaj Sah, Francesco Ferraguti, Andreas Lüthi

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1493-1500
Number of pages8
JournalNature Neuroscience
Issue number10
StatePublished - Oct 28 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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