Activation of ERK/MAP Kinase in the Amygdala Is Required for Memory Consolidation of Pavlovian Fear Conditioning

By G. Schafe, C. Atkins, M. Swank, E. Bauer, J. Sweatt, Joseph E LeDoux. Journal of Neuroscience, 2000

658 citations recorded by the source corpus.

Although much has been learned about the neurobiological mechanisms underlying Pavlovian fear conditioning at the systems and cellular levels, relatively little is known about the molecular mechanisms underlying fear memory consolidation. The present experiments evaluated the role of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling cascade in the amygdala during Pavlovian fear conditioning. We first show that ERK/MAPK is transiently activated–phosphorylated in the amygdala, specifically the lateral nucleus (LA), at 60 min, but not 15, 30, or 180 min, after conditioning, and that this activation is attributable to paired presentations of tone and shock rather than to nonassociative auditory stimulation, foot shock sensitization, or unpaired tone–shock presentations. We next show that infusions of U0126, an inhibitor of ERK/MAPK activation, aimed at the LA, dose-dependently impair long-term memory of Pavlovian fear conditioning but leaves short-term memory intact. Finally, we show that bath application of U0126 impairs long-term potentiation in the LA in vitro. Collectively, these results demonstrate that ERK/MAPK activation is necessary for both memory consolidation of Pavlovian fear conditioning and synaptic plasticity in the amygdala.

Subfields: Behavioral Neuroscience, Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/cf4a688fa4c9c7fbd9e326e79a29be25ff690042

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Citations in the corpus

Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. (2001, background): “Fifth, disruption of macromolecular synthesis in LA and surrounding areas prevents the consolidation of long-term memory for associative auditory fear conditioning (Bailey et al. 1999; Nader et al. 2000; Schafe et al. 2000), consistent with the widely held belief that macromolecular synthesis is ess”
Facilitation of Conditioned Fear Extinction by Systemic Administration or Intra-Amygdala Infusions of d-Cycloserine as Assessed with Fear-Potentiated Startle in Rats (2002, background): “…protein kinase inhibitor PD98059, as well as intra-amygdala PD98059 infusions, disrupt fear conditioning as assessed with both freezing (Schafe et al., 2000) and shock-motivated avoidance learning (Walz et al., 1999, 2000), respectively, and intra-amygdala PD98059 infusions also…”
Role of adrenal stress hormones in forming lasting memories in the brain. (2002, background): “ERK2 is considered critical for memory consolidation and long-term neuronal plasticity in both the amygdala and the hippocampus [63,64] and can be activated by noradrenergic stimulation and cAMP formation [65,66].”
MAPK cascade signalling and synaptic plasticity (2004, background): “, and LTP in the amygdala, which is associated with fear-dependent learnin”
Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear (2010, positive): “In contrast, early LTP and short-term fear memory were spared (165, 167, 449, 452).”
Cellular and systems reconsolidation in the hippocampus. (2002, positive): “McGill University auditory fear conditioning, which are stored in the amyg-Montreal, Quebec H3A 1B1 dala (Fanselow and LeDoux, 1999; Maren, 2001; Schafe et al., 2000 ), undergo protein synthesis-dependent re-”