Age-associated changes to neuronal dynamics involve a disruption of excitatory/inhibitory balance in C. elegans
- Boston University, United States
- University of Massachusetts Medical School, United States
- Brigham and Women's Hospital, United States
Abstract
In the aging brain, many of the alterations underlying cognitive and behavioral decline remain opaque. C. elegans offers a powerful model for aging research, with a simple, well-studied nervous system to further our understanding of the cellular modifications and functional alterations accompanying senescence. We perform multi-neuronal functional imaging across the aged C. elegans nervous system, measuring an age-associated breakdown in system-wide functional organization. At single-cell resolution, we detect shifts in activity dynamics toward higher frequencies. In addition, we measure a specific loss of inhibitory signaling that occurs early in the aging process and alters the systems critical excitatory/inhibitory balance. These effects are recapitulated with mutation of the calcium channel subunit UNC-2/CaV2a. We find that manipulation of inhibitory GABA signaling can partially ameliorate or accelerate the effects of aging. The effects of aging are also partially mitigated by disruption of the insulin signaling pathway, known to increase longevity, or by a reduction of caspase activation. Data from mammals are consistent with our findings, suggesting a conserved shift in the balance of excitatory/inhibitory signaling with age that leads to breakdown in global neuronal dynamics and functional decline.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Christopher V Gabel
Funding
National Institutes of Health (NIH R01 GM121457)
- Christopher W Connor
- Christopher V Gabel
National Institutes of Health (NIH R01 NS107475)
- Jeremy Florman
- Mark J Alkema
National Institutes of Health (NIH T32 GM008541)
- Gregory S Wirak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Wirak et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Age-associated changes to neuronal dynamics involve a disruption of excitatory/inhibitory balance in C. elegans
eLife 11:e72135.
https://doi.org/10.7554/eLife.72135
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