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Changes in presynaptic calcium signalling accompany age-related deficits in hippocampal LTP and cognitive impairment

Pereda, D.; Al-Osta, I.; Okorocha, A.E.; Easton, A.; Hartell, N.A.

Changes in presynaptic calcium signalling accompany age-related deficits in hippocampal LTP and cognitive impairment Thumbnail


Authors

D. Pereda

I. Al-Osta

A.E. Okorocha

N.A. Hartell



Abstract

The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long‐term potentiation requires stronger stimulation for induction in aged rats and mice and long‐term depression becomes more prevalent. An age‐dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age‐dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T‐maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired‐pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age‐dependent change in the properties or numbers of presynaptic calcium channels.

Citation

Pereda, D., Al-Osta, I., Okorocha, A., Easton, A., & Hartell, N. (2019). Changes in presynaptic calcium signalling accompany age-related deficits in hippocampal LTP and cognitive impairment. Aging Cell, 18(5), Article e13008. https://doi.org/10.1111/acel.13008

Journal Article Type Article
Acceptance Date Jun 26, 2019
Online Publication Date Jul 16, 2019
Publication Date Oct 31, 2019
Deposit Date Jul 10, 2019
Publicly Available Date Mar 29, 2024
Journal Aging Cell
Print ISSN 1474-9718
Electronic ISSN 1474-9726
Publisher Anatomical Society of Great Britain and Ireland
Peer Reviewed Peer Reviewed
Volume 18
Issue 5
Article Number e13008
DOI https://doi.org/10.1111/acel.13008

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Accepted Journal Article (Supplementary data) (236 Kb)
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Copyright Statement
Supplementary data © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.







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