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Publication : Impairments of spatial memory in an Alzheimer's disease model via degeneration of hippocampal cholinergic synapses.

First Author  Zhu H Year  2017
Journal  Nat Commun Volume  8
Issue  1 Pages  1676
PubMed ID  29162816 Mgi Jnum  J:256308
Mgi Id  MGI:6106273 Doi  10.1038/s41467-017-01943-0
Citation  Zhu H, et al. (2017) Impairments of spatial memory in an Alzheimer's disease model via degeneration of hippocampal cholinergic synapses. Nat Commun 8(1):1676
abstractText  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-beta 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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