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

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 Amanda 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), Heng‐Ye Man(Boston University), 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
November 16, 2017
10.1038/s41467-017-01943-0
Cited by 124Open Access
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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.

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