Conditioned stimulus presentations alter anxiety level in fear-conditioned mice

Mol Brain. 2019 Mar 29;12(1):28. doi: 10.1186/s13041-019-0445-4.

Abstract

It is generally believed that fear is rapidly triggered by a distinct cue while anxiety onset is less precise and not associated with a distinct cue. Although it has been claimed that both processes can be measured with certain independence of each other, it is unclear how exactly they differ. In this study, we measured anxiety in mice that received discriminative fear conditioning using behavioral, heart rate and calcium (Ca2+) responses in the ventral hippocampal CA1 (vCA1) neurons. We found that the occurrence of fear significantly interfered with anxiety measurements under various conditions. Diazepam reduced basal anxiety level but had no effect during the presentation of conditioned stimulus (CS). Injection of an inhibitory peptide of PKMzeta (ZIP) into the basolateral amygdala almost entirely abolished CS-triggered fear expression and reduced anxiety to basal level. Heart rate measures suggested a small reduction in anxiety during CS-. Calcium responses in the lateral hypothalamus-projecting vCA1 neurons showed a steady decay during CS suggesting a reduced anxiety. Thus, under our experimental conditions, CS presentations likely reduce anxiety level in the fear-conditioned mice.

Keywords: Amygdala; Calcium imaging; Diazepam; Discriminative fear conditioning; Heart rate; PKMzeta; Ventral hippocampal CA1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Anxiety / pathology
  • Anxiety / physiopathology*
  • Calcium / metabolism
  • Cell-Penetrating Peptides
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Diazepam / pharmacology
  • Diazepam / therapeutic use
  • Discrimination, Psychological
  • Fear / drug effects
  • Fear / physiology*
  • Freezing Reaction, Cataleptic / physiology
  • Heart Rate / drug effects
  • Hypothalamus / drug effects
  • Hypothalamus / pathology
  • Hypothalamus / physiopathology
  • Lipopeptides / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism

Substances

  • Cell-Penetrating Peptides
  • Lipopeptides
  • zeta-inhibitory peptide
  • protein kinase C zeta
  • Protein Kinase C
  • Diazepam
  • Calcium