title: The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise.
abstract: Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS.
authors.affiliation: Department of Psychology, Memory Development and Disorders Laboratory, University of Arizona, Tucson, Arizona.|Department of Educational Psychology, University of Nebraska, Lincoln, Nebraska.
authors.forename: Caron A C
authors.initials: CAC
authors.lastname: Clark
authors.affiliation: Department of Psychology, BIO5 and McKnight Brain Research Institutes, University of Arizona, Tucson, Arizona.|Department of Neurology, BIO5 and McKnight Brain Research Institutes, University of Arizona, Tucson, Arizona.
authors.forename: Fabian
authors.initials: F
authors.lastname: Fernandez
authors.affiliation: Department of Psychology, Memory Development and Disorders Laboratory, University of Arizona, Tucson, Arizona.
authors.forename: Stella
authors.initials: S
authors.lastname: Sakhon
authors.affiliation: Department of Psychology, Memory Development and Disorders Laboratory, University of Arizona, Tucson, Arizona.
authors.forename: Goffredina
authors.initials: G
authors.lastname: Spanò
authors.affiliation: Department of Psychology, Memory Development and Disorders Laboratory, University of Arizona, Tucson, Arizona.
authors.forename: Jamie O
authors.initials: JO
authors.lastname: Edgin
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D018891:Dentate Gyrus / Q000503:physiopathology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D057170:Translational Research, Biomedical; D055815:Young Adult
keywords: Down syndrome; hippocampus; object recognition; spatial memory; trisynaptic circuit