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.
Highlights
Aging Cell published by the Anatomical Society and John Wiley Sons Ltd
Behavioural experiments In order to establish over what age range hippocampal function becomes impaired in mice incorporating the SyGCaMP2-mCherry transgene, groups of male and female mice aged in groups of 6, 12, 18 and 24 months underwent a series of different cognitive behavioural tasks which have previously been shown to require various degrees of hippocampal processing
In the spontaneous object recognition (SOR) task, two identical copies of the same object were placed in the object area and the mouse was allowed to interact with them for two minutes, after which the lateral guillotine doors were opened and the animal shuttled back to the holding area for one minute, while one of the copies of the object was replaced for a different one
Summary
Citation for published item: Pereda, D. and Al-Osta, I. and Okorocha, A.E. and Easton, A. and Hartell, N.A. (2019) 'Changes in presynaptic calcium signalling accompany age-related decits in hippocampal LTP and cognitive impairment.', Aging cell., 18 (5). e13008. Aging Cell published by the Anatomical Society and John Wiley Sons Ltd. Aging Cell published by the Anatomical Society and John Wiley Sons Ltd The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:. A full bibliographic reference is made to the original source a link is made to the metadata record in DRO the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Durham University Library, Stockton Road, Durham DH1 3LY, United Kingdom Tel : +44 (0)191 334 3042 | Fax : +44 (0)191 334 2971 https://dro.dur.ac.uk
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