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J Neurosci. 2018 Apr 18;38(16):3911-3928. doi: 10.1523/JNEUROSCI.2513-17.2018. Epub 2018 Mar 26.

Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.

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Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
Sleep and Circadian Neuroscience Institute, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, Oxford OX1 3RE, UK, and.
Eli Lilly & Company Ltd, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK,


Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture.SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we performed chronic electrophysiological recordings of cortical neural activity during waking, sleep, and after sleep deprivation from young and older mice. We found that all main hallmarks of cortical activity during spontaneous sleep and recovery sleep after sleep deprivation were largely intact in older mice, suggesting that the well-described age-related changes in global sleep are unlikely to arise from a disruption of local network dynamics within the neocortex.


aging; mice; neocortex; sleep

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