Neuronal circuits of fear extinction
European Journal of Neuroscience. 2010-02-01; 31(4): 599-612
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1. Eur J Neurosci. 2010 Feb;31(4):599-612. doi: 10.1111/j.1460-9568.2010.07101.x.
Epub 2010 Feb 11.
Neuronal circuits of fear extinction.
Herry C(1), Ferraguti F, Singewald N, Letzkus JJ, Ehrlich I, Lüthi A.
(1)INSERM U862, Neurocentre Magendie, Bordeaux, France.
Fear extinction is a form of inhibitory learning that allows for the adaptive
control of conditioned fear responses. Although fear extinction is an active
learning process that eventually leads to the formation of a consolidated
extinction memory, it is a fragile behavioural state. Fear responses can recover
spontaneously or subsequent to environmental influences, such as context changes
or stress. Understanding the neuronal substrates of fear extinction is of
tremendous clinical relevance, as extinction is the cornerstone of psychological
therapy of several anxiety disorders and because the relapse of maladaptative
fear and anxiety is a major clinical problem. Recent research has begun to shed
light on the molecular and cellular processes underlying fear extinction. In
particular, the acquisition, consolidation and expression of extinction memories
are thought to be mediated by highly specific neuronal circuits embedded in a
large-scale brain network including the amygdala, prefrontal cortex, hippocampus
and brain stem. Moreover, recent findings indicate that the neuronal circuitry of
extinction is developmentally regulated. Here, we review emerging concepts of the
neuronal circuitry of fear extinction, and highlight novel findings suggesting
that the fragile phenomenon of extinction can be converted into a permanent
erasure of fear memories. Finally, we discuss how research on genetic animal
models of impaired extinction can further our understanding of the molecular and
genetic bases of human anxiety disorders.
PMID: 20384807 [Indexed for MEDLINE]