Impairments of spatial memory in an Alzheimer's disease model via degeneration of hippocampal cholinergic synapses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29162816.
- Also identified by DOI 10.1038/s41467-017-01943-0 and PMC identifier 5698429.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Alzheimer Disease
- Cholinergic Neurons
- Disease Models, Animal
- Hippocampus
- Spatial Memory
- Synapses