Increased c-fos expression in the central nucleus of the amygdala and enhancement of cued fear memory in Dyt1 DeltaGAG knock-in mice.
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.
Yokoi
Fumiaki
F
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Dang
Mai T
MT
Miller
Courtney A
CA
Marshall
Andrea G
AG
Campbell
Susan L
SL
Sweatt
J David
JD
Li
Yuqing
Y
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001362:Avoidance Learning / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D003463:Cues; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005239:Fear / Q000502:physiology*; D005260:Female; D055879:Gene Knock-In Techniques; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
D015415:Biomarkers; C491548:Dyt1 protein, mouse; D018832:Molecular Chaperones; D016760:Proto-Oncogene Proteins c-fos