Hippocampal encoding of interoceptive context during fear conditioning

Transl Psychiatry. 2017 Jan 3;7(1):e991. doi: 10.1038/tp.2016.254.

Abstract

Rodent models of auditory fear conditioning are often used to understand the molecular mechanisms regulating fear- and anxiety-related behaviors. Conditioning and extinction memories are influenced by contextual cues, and the reinstatement of conditioned fear occurs when the conditioning stimulus is presented in a context different from the extinction context. Although it has been proposed that internal state is a feature of context that could influence extinction, contributions of interoception to conditioning have not been experimentally addressed. Here we use ethanol (EtOH) to show that interoceptive cues are encoded through the hippocampus by mechanisms that involve increased phosphorylation of GluR1 on serine 845, and biophysical alterations in neuronal membranes that facilitate stabilization of surface-located calcium-permeable n-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor (AMPAR) into membrane microdomains. Conflicting interoceptive cues during extinction and fear relapse testing resulted in a failure to consolidate extinction that was reversed by the administration of AMPAR antagonists immediately following the retrieval cue.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Benzodiazepines / pharmacology
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology*
  • Conditioning, Psychological / drug effects*
  • Cues
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • Extinction, Psychological / drug effects*
  • Fear*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Mice
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nitriles
  • Pyridones / pharmacology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / drug effects*
  • Receptors, AMPA / metabolism
  • Self Administration

Substances

  • Central Nervous System Depressants
  • Nitriles
  • Pyridones
  • Receptors, AMPA
  • Benzodiazepines
  • Ethanol
  • talampanel
  • perampanel
  • glutamate receptor ionotropic, AMPA 1