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

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posted on 18.09.2019, 09:26 by Daniel Pereda, Ibrahim Al-Osta, Albert E. Okorocha, Alexander Easton, Nicholas A. Hartell
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.

Funding

This work was supported by Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/K008382/1, BB/M012034/1 and BB/L00691X/1 to NH. The authors would like to thank Michele Chan for help setting up the SOR/SOL test.

History

Citation

Aging Cell, 2019, 18 (5), e13008

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Neuroscience, Psychology and Behaviour

Version

VoR (Version of Record)

Published in

Aging Cell

Publisher

Wiley for Anatomical Society of Great Britain and Ireland

eissn

1474-9726

Acceptance date

26/06/2019

Copyright date

2019

Available date

18/09/2019

Publisher version

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13008

Notes

Additional supporting information may be found online in the Supporting Information section at the end of the article.

Language

en