Increased c-fos expression in the central nucleus of the amygdala and enhancement of cued fear memory in Dyt1 DeltaGAG knock-in mice

Neurosci Res. 2009 Nov;65(3):228-35. doi: 10.1016/j.neures.2009.07.004. Epub 2009 Jul 18.

Abstract

DYT1 dystonia is caused by a trinucleotide deletion of GAG (DeltaGAG) in DYT1, which codes for torsinA. A previous epidemiologic study suggested an association of DYT1 DeltaGAG mutation with early-onset recurrent major depression. However, another study reported no significant association with depression, but instead showed an association with anxiety and dystonia. In this study, we analyzed these related behaviors in Dyt1 DeltaGAG heterozygous knock-in mice. The knock-in mice showed a subtle anxiety-like behavior but did not show depression-like behaviors. The mutant mice also displayed normal sensorimotor gating function in a prepulse inhibition test. While normal hippocampus-dependent contextual fear memory and hippocampal CA1 long-term potentiation (LTP) were observed, the knock-in mice exhibited an enhancement in the formation of cued fear memories. Anatomical analysis indicated that the number of c-fos positive cells was significantly increased while the size of the central nucleus of the amygdala (CE) was significantly reduced in the knock-in mice. These results suggest that the Dyt1 DeltaGAG mutation increased the activity of the CE and enhanced the acquisition of the cued fear memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism*
  • Animals
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology
  • Atrophy / genetics
  • Atrophy / metabolism
  • Atrophy / physiopathology
  • Avoidance Learning / physiology
  • Biomarkers / metabolism
  • Cell Count
  • Cues
  • Depressive Disorder / genetics
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Dystonia / genetics*
  • Dystonia / metabolism
  • Dystonia / physiopathology
  • Fear / physiology*
  • Female
  • Gene Knock-In Techniques
  • Hippocampus / physiology
  • Long-Term Potentiation / genetics
  • Male
  • Memory / physiology*
  • Mice
  • Molecular Chaperones / genetics*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Proto-Oncogene Proteins c-fos / metabolism

Substances

  • Biomarkers
  • Dyt1 protein, mouse
  • Molecular Chaperones
  • Proto-Oncogene Proteins c-fos