Format

Send to

Choose Destination
Mol Neurodegener. 2017 Nov 14;12(1):86. doi: 10.1186/s13024-017-0228-2.

Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer's disease.

Bai Y1,2, Li M1, Zhou Y1,2, Ma L1, Qiao Q1, Hu W1, Li W1, Wills ZP3, Gan WB4,5.

Author information

1
Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
2
Skirball Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY, 10016, USA.
3
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
4
Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. gan@saturn.med.nyu.edu.
5
Skirball Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY, 10016, USA. gan@saturn.med.nyu.edu.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD.

METHODS:

We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice. We also performed calcium imaging to determine the effect of Aβ oligomers on dendritic calcium activity. In addition, structural and functional two-photon imaging were used to examine the link between abnormal dendritic calcium activity and changes in dendritic spine size in the AD mouse model.

RESULTS:

We found that somatic calcium activities of layer 2/3 neurons were significantly lower in the primary motor cortex of 3-month-old APPswe/PS1dE9 mice than in wild type mice during quiet resting, but not during running on a treadmill. Notably, a significantly larger fraction of apical dendrites of layer 2/3 pyramidal neurons showed calcium transients with abnormally long duration and high peak amplitudes during treadmill running in AD mice. Administration of Aβ oligomers into the brain of wild type mice also induced abnormal dendritic calcium transients during running. Furthermore, we found that the activity and size of dendritic spines were significantly reduced on dendritic branches with abnormally prolonged dendritic calcium transients in AD mice.

CONCLUSION:

Our findings show that abnormal dendritic calcium transients and synaptic depotentiation occur before amyloid plaque formation in the motor cortex of the APPswe/PS1dE9 mouse model of AD. Dendritic calcium transients with abnormally long durations and high amplitudes could be induced by soluble Aβ oligomers and contribute to synaptic deficits in the early pathogenesis of AD.

KEYWORDS:

APPswe/PS1dE9; Alzheimer’s disease; Dendritic calcium activity; Soluble Aβ oligomers; Synaptic depotentiation; Two-photon imaging

PMID:
29137651
PMCID:
PMC5686812
DOI:
10.1186/s13024-017-0228-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center