Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia

Casey Cook, Judy H. Dunmore, Melissa E. Murray, Kristyn Scheffel, Nawsheen Shukoor, Jimei Tong, Monica Castanedes-Casey, Virginia Phillips, Linda Rousseau, Michael S. Penuliar, Aishe Kurti, Dennis W. Dickson, Leonard Petrucelli, John D. Fryer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1769-1777
Number of pages9
JournalNeurobiology of aging
Volume35
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • Amygdala
  • Frontotemporal dementia
  • Neurodegeneration
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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