Abstract
Deficits in hippocampal cellular and synaptic plasticity are frequently associated with cognitive and mood disorders, and indeed common mechanisms of antidepressants are thought to involve neuroplastic processes. Here, we investigate hippocampal adult-born cell survival and synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in serotonin transporter (5-HTT) knockout (KO) mice. From 8 weeks of age, mice either continued in standard-housing conditions or were given access to voluntary running wheels for 1 month. Electrophysiology was performed on hippocampal slices to measure LTP and LTD, and immunohistochemistry was used to assess cell proliferation and subsequent survival in the dentate gyrus. The results revealed a reduced LTP in 5-HTT KO mice that was restored to wild-type (WT) levels after chronic exercise. While LTD appeared normal in 5-HTT KO, exercise decreased the magnitude of LTD in both WT and 5-HTT KO mice. Furthermore, although 5-HTT KO mice had normal hippocampal adult-born cell survival, they did not benefit from the pro-proliferative effects of exercise observed in WT animals. Taken together, these findings suggest that reduced 5-HTT expression is associated with significant alterations to functional neuroplasticity. Interestingly, 5-HTT appeared necessary for exercise-induced augmentation of adult-born hippocampal cell survival, yet exercise corrected the LTP impairment displayed by 5-HTT KO mice. Together, our findings further highlight the salience of serotonergic signalling in mediating the neurophysiological benefits of exercise.
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The data described in this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank Volkan Uzungil for acquiring the representative microscopy images used in this manuscript.
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This work was supported by an Australian Research Council (ARC) Discovery Early Career Research Award (TR). AJH is a National Health and Medical Research Council (NHMRC) Principal Research Fellow. The Florey Institute of Neuroscience and Mental Health acknowledges the support from the Victorian Government’s Operational Infrastructure Support Grant.
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JR and TR conceived the study. JR, FC, PA, CW and TR were involved in data collection and analysis. SL genotyped all animals. CW prepared the manuscript, while TR and AJH provided critical feedback and revisions.
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All procedures were approved by the Florey Institute of Neuroscience and Mental Health Animal Ethics Committee and adhered with the guidelines published by the National Health and Medical Research Council (NHMRC).
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Wilson, C., Rogers, J., Chen, F. et al. Exercise ameliorates aberrant synaptic plasticity without enhancing adult-born cell survival in the hippocampus of serotonin transporter knockout mice. Brain Struct Funct 226, 1991–1999 (2021). https://doi.org/10.1007/s00429-021-02283-y
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DOI: https://doi.org/10.1007/s00429-021-02283-y