Extinction of auditory fear conditioning requires MAPK/ERK activation in the basolateral amygdala
European Journal of Neuroscience. 2006-07-01; 24(1): 261-269
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1. Eur J Neurosci. 2006 Jul;24(1):261-9.
Extinction of auditory fear conditioning requires MAPK/ERK activation in the
Herry C(1), Trifilieff P, Micheau J, Lüthi A, Mons N.
(1)Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux
I, Avenue des Facultés, 33405 Talence, France.
Whereas the neuronal substrates underlying the acquisition of auditory fear
conditioning have been widely studied, the substrates and mechanisms mediating
the acquisition of fear extinction remain largely elusive. Previous reports
indicate that consolidation of fear extinction depends on the mitogen-activated
protein kinase/extracellular-signal regulated kinase (MAPK/ERK) signalling
pathway and on protein synthesis in the medial prefrontal cortex (mPFC). Based on
experiments using the fear-potentiated startle paradigm suggesting a role for
neuronal plasticity in the basolateral amygdala (BLA) during fear extinction, we
directly addressed whether MAPK/ERK signalling in the basolateral amygdala is
necessary for the acquisition of fear extinction using conditioned freezing as a
read-out. First, we investigated the regional and temporal pattern of MAPK/ERK
activation in the BLA following extinction learning in C57Bl/6J mice. Our results
indicate that acquisition of extinction is associated with an increase of
phosphorylated MAPK/ERK in the BLA. Moreover, we found that inhibition of the
MAPK/ERK signalling pathway by intrabasolateral amygdala infusion of the MEK
inhibitor, U0126, completely blocks acquisition of extinction. Thus, our results
indicate that the MAPK/ERK signalling pathway is required for extinction of
auditory fear conditioning in the BLA, and support a role for neuronal plasticity
in the BLA during the acquisition of fear extinction.
PMID: 16882022 [Indexed for MEDLINE]