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Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses

Author

Listed:
  • Houze Zhu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Huanhuan Yan

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Na Tang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xinyan Li

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Pei Pang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Hao Li

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Wenting Chen

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Yu Guo

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Shu Shu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • You Cai

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Lei Pei

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Dan Liu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Min-Hua Luo

    (Chinese Academy of Sciences)

  • Hengye Man

    (Huazhong University of Science and Technology
    Boston University)

  • Qing Tian

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Yangling Mu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Ling-Qiang Zhu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Youming Lu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

Abstract

Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival.

Suggested Citation

  • Houze Zhu & Huanhuan Yan & Na Tang & Xinyan Li & Pei Pang & Hao Li & Wenting Chen & Yu Guo & Shu Shu & You Cai & Lei Pei & Dan Liu & Min-Hua Luo & Hengye Man & Qing Tian & Yangling Mu & Ling-Qiang Zhu, 2017. "Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01943-0
    DOI: 10.1038/s41467-017-01943-0
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    Cited by:

    1. Qingtao Sun & Jianping Zhang & Anan Li & Mei Yao & Guangcai Liu & Siqi Chen & Yue Luo & Zhi Wang & Hui Gong & Xiangning Li & Qingming Luo, 2022. "Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Feng Xiong & Hong Yang & Yi-Ge Song & Hai-Bin Qin & Qing-Yang Zhang & Xian Huang & Wei Jing & Manfei Deng & Yang Liu & Zhixiang Liu & Yin Shen & Yunyun Han & Youming Lu & Xiangmin Xu & Todd C. Holmes , 2022. "An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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