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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Contrasting contribution of resident and repopulated brain macrophages in sustaining sleep-wake circuitry
Ali Seifinejad1,2, Mojtaba Bandarabadi3, Meriem Haddar3
1Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. ali.seifinejad@mail.ch.
Abstract:
Sleep is a complex behavior regulated by various brain cell types. However, the roles of brain-resident macrophages, including microglia and CNS-associated macrophages (CAMs), particularly those derived postnatally, in sleep regulation remain poorly understood. Here, we investigated the effects of resident (embryo-derived) and repopulated (postnatally derived) brain-resident macrophages on the regulation of vigilance states in mice. We found that depletion in resident brain macrophages caused increased sleep in the active period, but reduced its quality, reflected in reduced power of brain sleep oscillations. This was observed both for the Non-REM and REM sleep stages. Subsequent repopulation by postnatal brain macrophages resulted in altered, but not fully restored, sleep-wake patterns and additionally induced sleep fragmentation. Furthermore, brain macrophage depletion caused excitatory-inhibitory synaptic imbalance, which was resistant to repopulation, and led to increased inhibitory synapses. At the metabolite level, the distinct metabolite profile induced by brain macrophage depletion largely returned to normal after repopulation. Our findings suggest a so far largely unknown interaction between brain-resident macrophages and sleep and highlight functional differences between resident and postnatally-derived repopulated brain macrophages, paving the way to future exploration of the role of brain macrophages of different origin in sleep disorders and synaptic connectivity.
Insights
Resident brain macrophages significantly impact sleep quality and brain oscillations. Postnatal repopulation alters sleep patterns and induces fragmentation, suggesting distinct roles for macrophages of different origins in sleep regulation.
Area of Science:
- Neuroscience
- Immunology
- Sleep Science
Background:
- Brain-resident macrophages, including microglia and CNS-associated macrophages (CAMs), are crucial for brain function.
- The specific roles of resident (embryo-derived) and repopulated (postnatally derived) brain macrophages in sleep regulation are not well understood.
Purpose of the Study:
- To investigate the impact of resident and repopulated brain macrophages on vigilance states and sleep regulation in mice.
- To explore the functional differences between embryo-derived and postnatally-derived brain macrophages in the context of sleep.
Main Methods:
- Depletion of resident brain macrophages in mice.
- Repopulation of brain macrophages with postnatal-derived cells.
- Analysis of sleep-wake patterns, including Non-REM and REM sleep stages.
- Assessment of brain oscillations, synaptic function (excitatory-inhibitory balance), and metabolite profiles.
Main Results:
- Depletion of resident brain macrophages increased sleep during the active period but reduced sleep quality, indicated by decreased brain sleep oscillation power.
- Repopulation with postnatal macrophages led to altered sleep-wake patterns and induced sleep fragmentation.
- Brain macrophage depletion caused an excitatory-inhibitory synaptic imbalance, characterized by increased inhibitory synapses, which persisted after repopulation.
- Metabolite profiles normalized after repopulation, suggesting partial functional recovery.
Conclusions:
- Brain-resident macrophages play a significant, previously unrecognized role in regulating sleep.
- Functional differences exist between resident (embryo-derived) and repopulated (postnatally-derived) brain macrophages concerning sleep regulation and synaptic function.
- These findings open new avenues for understanding the role of brain macrophages in sleep disorders and synaptic plasticity.
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