Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer's disease.
Patients with Alzheimer's disease (AD) suffer from impaired memory and emotional disturbances, the pathogenesis of which is not entirely clear. In APP/PS1 transgenic mice, a model of AD in which amyloid beta (Abeta) accumulates in the brain, we have examined neurons in the lateral nucleus of the amygdala (LA), a brain region crucial to establish cued fear conditioning. We found that although there was no neuronal loss in this region and Abeta plaques only occupy less than 1% of its volume, these mice froze for shorter times after auditory fear conditioning when compared to their non-transgenic littermates. We performed a three-dimensional analysis of projection neurons and of thousands of dendritic spines in the LA. We found changes in dendritic tree morphology and a substantial decrease in the frequency of large spines in plaque-free neurons of APP/PS1 mice. We suggest that these morphological changes in the neurons of the LA may contribute to the impaired auditory fear conditioning seen in this AD model.
Knafo
Shira
S
Instituto Cajal (CSIC), Madrid, Spain.
Venero
Cesar
C
Merino-Serrais
Paula
P
Fernaud-Espinosa
Isabel
I
Gonzalez-Soriano
Juncal
J
Ferrer
Isidro
I
Santpere
Gabriel
G
DeFelipe
Javier
J
D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D000679:Amygdala / Q000648:ultrastructure*; D000818:Animals; D003214:Conditioning, Classical; D049229:Dendritic Spines / Q000648:ultrastructure*; D005239:Fear; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D023421:Models, Animal; D009473:Neuronal Plasticity; D058225:Plaque, Amyloid / Q000648:ultrastructure