title: Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia.
abstract: Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17.
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Casey
authors: C
authors: Cook
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Judy H
authors: JH
authors: Dunmore
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Melissa E
authors: ME
authors: Murray
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Kristyn
authors: K
authors: Scheffel
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Nawsheen
authors: N
authors: Shukoor
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Jimei
authors: J
authors: Tong
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Monica
authors: M
authors: Castanedes-Casey
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Virginia
authors: V
authors: Phillips
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Linda
authors: L
authors: Rousseau
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Michael S
authors: MS
authors: Penuliar
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors: Aishe
authors: A
authors: Kurti
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA; Neurobiology of Disease Program, Mayo Graduate School, Rochester, MN, USA.
authors: Dennis W
authors: DW
authors: Dickson
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA; Neurobiology of Disease Program, Mayo Graduate School, Rochester, MN, USA.
authors: Leonard
authors: L
authors: Petrucelli
authors: Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA; Neurobiology of Disease Program, Mayo Graduate School, Rochester, MN, USA. Electronic address: fryer.john@mayo.edu.
authors: John D
authors: JD
authors: Fryer
mesh_terms: D000679:Amygdala / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005239:Fear; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D007802:Language; D007858:Learning; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009410:Nerve Degeneration; D012720:Severity of Illness Index; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Amygdala; Frontotemporal dementia; Neurodegeneration; Tau; Tauopathy