title: Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Instituto Cajal (CSIC), Madrid, Spain.
authors.forename: Shira
authors.initials: S
authors.lastname: Knafo
authors.forename: Cesar
authors.initials: C
authors.lastname: Venero
authors.forename: Paula
authors.initials: P
authors.lastname: Merino-Serrais
authors.forename: Isabel
authors.initials: I
authors.lastname: Fernaud-Espinosa
authors.forename: Juncal
authors.initials: J
authors.lastname: Gonzalez-Soriano
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Gabriel
authors.initials: G
authors.lastname: Santpere
authors.forename: Javier
authors.initials: J
authors.lastname: DeFelipe
mesh_terms: 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