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Articles, Systems/Circuits

Progressive Functional Impairments of Hippocampal Neurons in a Tauopathy Mouse Model

Sarah M. Ciupek, Jingheng Cheng, Yousuf O. Ali, Hui-Chen Lu and Daoyun Ji
Journal of Neuroscience 27 May 2015, 35 (21) 8118-8131; DOI: https://doi.org/10.1523/JNEUROSCI.3130-14.2015
Sarah M. Ciupek
1Department of Molecular and Cellular Biology,
2Department of Neuroscience, and
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Jingheng Cheng
1Department of Molecular and Cellular Biology,
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Yousuf O. Ali
3Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, and
4The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030
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Hui-Chen Lu
2Department of Neuroscience, and
3Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, and
4The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030
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Daoyun Ji
1Department of Molecular and Cellular Biology,
2Department of Neuroscience, and
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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.

  • Alzheimer's
  • learning and memory
  • neurodegeneration
  • place cells
  • tau
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The Journal of Neuroscience: 35 (21)
Journal of Neuroscience
Vol. 35, Issue 21
27 May 2015
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Progressive Functional Impairments of Hippocampal Neurons in a Tauopathy Mouse Model
Sarah M. Ciupek, Jingheng Cheng, Yousuf O. Ali, Hui-Chen Lu, Daoyun Ji
Journal of Neuroscience 27 May 2015, 35 (21) 8118-8131; DOI: 10.1523/JNEUROSCI.3130-14.2015

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Progressive Functional Impairments of Hippocampal Neurons in a Tauopathy Mouse Model
Sarah M. Ciupek, Jingheng Cheng, Yousuf O. Ali, Hui-Chen Lu, Daoyun Ji
Journal of Neuroscience 27 May 2015, 35 (21) 8118-8131; DOI: 10.1523/JNEUROSCI.3130-14.2015
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Keywords

  • Alzheimer's
  • learning and memory
  • neurodegeneration
  • place cells
  • tau

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