Elsevier

Neuroscience

Volume 106, Issue 2, 6 September 2001, Pages 255-261
Neuroscience

Circadian rhythms in firing rate of individual suprachiasmatic nucleus neurons from adult and middle-aged mice

https://doi.org/10.1016/S0306-4522(01)00285-8Get rights and content

Abstract

The suprachiasmatic nucleus contains a biological clock that drives circadian rhythms in vivo and in vitro. It has been suggested that the suprachiasmatic nucleus is a primary target of the aging process, because age-related changes in behavioral rhythms are mirrored in alterations in circadian pacemaker function. Using long-term, single-cell recording, we assessed the effect of age on firing-rate patterns of individual suprachiasmatic nucleus neurons of young adult (2–4 months) and middle-aged (9–11 months) C3H mice. Individual suprachiasmatic nucleus neurons from adult mice maintained in culture for at least one week exhibited robust circadian rhythms in spontaneous activity that were similar in the free-running period (23.7±0.3 h mean±S.E.M.) to recordings from neurons dispersed from neonatal tissue, and showed evidence of entrainment to prior light cycles by exhibiting peak activity, in vitro, approximately 4.0±0.3 h (mean±S.E.M.) after the time of expected light onset. Aging led to a decreased amplitude of impulse activity in dispersed suprachiasmatic nucleus neurons and increased variability in the circadian waveform.

From these results we suggest that age-related deterioration in circadian clock function occurs at the level of individual cells, which may account for some of the age-related deficits observed in the expression of behavioral rhythmicity.

Section snippets

Animals and behavioral analysis

Male C3H mice (Charles River Laboratories, Wilmington, MA, USA) were group-housed under a 12:12 LD cycle and given free access to food and water in a temperature-controlled (22–24°C) environment for at least 15 days prior to experimentation. According to the estimated life span of male C3H mice maintained in animal facilities (13.4±0.2 months, Green, 1975), animals were classified into two groups: young adult (2–4 months) and middle-aged (9–11 months). Animals (n=16 young and 18 middle-aged)

Results

Aging from approximately 3–10 months altered the pattern and the period of locomotor activity rhythms of mice. Young adult mice expressed a clear rhythm in wheel-running activity in both LD and DD conditions (Fig. 1A), and the period of free-running activity was slightly shorter than 24 h in each case. Although the actograms generated from wheel-running activity of middle-aged mice appeared fragmented, an estimation of the free-running period with a confidence level of 0.01 could be performed

Discussion

This is the first report of successful long-duration electrical recording of individual adult SCN neurons. Our results demonstrate that a circadian rhythm in firing rate can be recorded from individual SCN neurons from mice as old as 11 months for up to 5 days in vitro. The rhythm in firing rate is altered significantly in 9–11-month-old mice when compared to mice of 2–4 months of age.

Previous studies have developed methods for culturing adult neurons from brain areas outside the SCN for

Acknowledgements

We wish to thank Edwin Spenceley for technical assistance, Thomas Breeden for programming the data-acquisition system, Martin Straume for statistical advice, and Naomi Ihara and Michael Menaker for assistance with behavioral assays. This research was supported by Grants from the Association Française pour la Recherche Thérapeutique (AFRT), the Philippe Foundation, the National Institutes of Health (NIH NS15264) and the NSF Center for Biological Timing.

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