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

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 () and Youming Lu ()
Additional contact information
Houze Zhu: Huazhong University of Science and Technology
Huanhuan Yan: Huazhong University of Science and Technology
Na Tang: Huazhong University of Science and Technology
Xinyan Li: Huazhong University of Science and Technology
Pei Pang: Huazhong University of Science and Technology
Hao Li: Huazhong University of Science and Technology
Wenting Chen: Huazhong University of Science and Technology
Yu Guo: Huazhong University of Science and Technology
Shu Shu: Huazhong University of Science and Technology
You Cai: Huazhong University of Science and Technology
Lei Pei: Huazhong University of Science and Technology
Dan Liu: Huazhong University of Science and Technology
Min-Hua Luo: Chinese Academy of Sciences
Hengye Man: Huazhong University of Science and Technology
Qing Tian: Huazhong University of Science and Technology
Yangling Mu: Huazhong University of Science and Technology
Ling-Qiang Zhu: Huazhong University of Science and Technology
Youming Lu: Huazhong University of Science and Technology

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01943-0

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