title: Progressive functional impairments of hippocampal neurons in a tauopathy mouse model.
abstract: The age-dependent progression of tau pathology is a major characteristic of tauopathies, including Alzheimer's disease (AD), and plays an important role in the behavioral phenotypes of AD, including memory deficits. Despite extensive molecular and cellular studies on tau pathology, it remains to be determined how it alters the neural circuit functions underlying learning and memory in vivo. In rTg4510 mice, a Tau-P301L tauopathy model, hippocampal place fields that support spatial memories are abnormal at old age (7-9 months) when tau tangles and neurodegeneration are extensive. However, it is unclear how the abnormality in the hippocampal circuit function arises and progresses with the age-dependent progression of tau pathology. Here we show that in young (2-4 months of age) rTg4510 mice, place fields of hippocampal CA1 cells are largely normal, with only subtle differences from those of age-matched wild-type control mice. Second, high-frequency ripple oscillations of local field potentials in the hippocampal CA1 area are significantly reduced in young rTg4510 mice, and even further deteriorated in old rTg4510 mice. The ripple reduction is associated with less bursty firing and altered synchrony of CA1 cells. Together, the data indicate that deficits in ripples and neuronal synchronization occur before overt deficits in place fields in these mice. The results reveal a tau-pathology-induced progression of hippocampal functional changes in vivo.
authors.affiliation: Department of Molecular and Cellular Biology, Department of Neuroscience, and.
authors.forename: Sarah M
authors.identifier: http://orcid.org/0000-0002-2581-2094
authors.initials: SM
authors.lastname: Ciupek
authors.affiliation: Department of Molecular and Cellular Biology.
authors.forename: Jingheng
authors.identifier: http://orcid.org/0000-0003-0331-7284
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, and The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030.
authors.forename: Yousuf O
authors.initials: YO
authors.lastname: Ali
authors.affiliation: Department of Neuroscience, and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, and The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lu
authors.affiliation: Department of Molecular and Cellular Biology, Department of Neuroscience, and dji@bcm.edu.
authors.forename: Daoyun
authors.initials: D
authors.lastname: Ji
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D024801:Tauopathies / Q000473:pathology / Q000503:physiopathology*
keywords: Alzheimer's; learning and memory; neurodegeneration; place cells; tau