Hippocampal Erk mechanisms linking prediction error to fear extinction: Roles of shock expectancy and contextual aversive valence

Kyu Hwan Huh, Yomayra F. Guzman, Natalie C. Tronson, Anita L. Guedea, Can Gao, Jelena Radulovic

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Extinction of fear requires learning that anticipated aversive events no longer occur. Animal models reveal that sustained phosphorylation of the extracellular signal-regulated kinase (Erk) in hippocampal CA1 neurons plays an important role in this process. However, the key signals triggering and regulating the activity of Erk are not known. By varying the degree of expected and delivered aversive reinforcement, we demonstrate that Erk specifically responds to prediction errors of contextual aversive events. An increase of somatonudear phospho-Erk (pErk) within principal CA1 neurons was observed only when the expectation of contextual foot shock was violated, but not when the context was consistently nonreinforced or reinforced by foot shock. The rate of error detection, Erk signaling, and fear extinction markedly depended on shock expectancy and the aversive valence of the context, as revealed by comparison of groups trained with single, continuous, or partial reinforcement. On the basis of these findings, the hippocampal Erk response to prediction errors of aversive outcome is proposed as a unique mechanism of fear extinction. Improving the detection and processing of these errors has the potential to attenuate fear responses in patients with anxiety disorders.

Original languageEnglish (US)
Pages (from-to)273-278
Number of pages6
JournalLearning and Memory
Volume16
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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