Neurobiological correlates of state-dependent context fear

Mariah A.A. Meyer, Kevin A. Corcoran, Helen J. Chen, Sonia Gallego, Guanguan Li, Veda V. Tiruveedhula, James M. Cook, Jelena Radulovic*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Retrieval of fear memories can be state-dependent, meaning that they are best retrieved if the brain states at encoding and retrieval are similar. Such states can be induced by activating extrasynaptic γ-aminobutyric acid type A receptors (GABAAR) with the broad α-subunit activator gaboxadol. However, the circuit mechanisms and specific subunits underlying gaboxadol's effects are not well understood. Here we show that gaboxadol induces profound changes of local and network oscillatory activity, indicative of discoordinated hippocampal-cortical activity, that were accompanied by robust and long-lasting state-dependent conditioned fear. Episodic memories typically are hippocampus-dependent for a limited period after learning, but become cortex-dependent with the passage of time. In contrast, state-dependent memories continued to rely on hippocampal GABAergic mechanisms for memory retrieval. Pharmacological approaches with α- subunit-specific agonists targeting the hippocampus implicated the prototypic extrasynaptic subunits (α4) as the mediator of state-dependent conditioned fear. Together, our findings suggest that continued dependence on hippocampal rather than cortical mechanisms could be an important feature of state-dependent memories that contributes to their conditional retrieval.

Original languageEnglish (US)
Pages (from-to)385-391
Number of pages7
JournalLearning and Memory
Volume24
Issue number9
DOIs
StatePublished - Sep 2017

ASJC Scopus subject areas

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

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    Meyer, M. A. A., Corcoran, K. A., Chen, H. J., Gallego, S., Li, G., Tiruveedhula, V. V., Cook, J. M., & Radulovic, J. (2017). Neurobiological correlates of state-dependent context fear. Learning and Memory, 24(9), 385-391. https://doi.org/10.1101/lm.045542.117