With the current society's focus on high productivity and performance, impaired sleep regimen has become prevalent, affecting as much as 25% of the adult population. Sleep loss can lead to many detrimental consequences, including cognitive impairments. In the brain, the hippocampus is one of the regions most vulnerable to sleep deprivation (SD), often displaying neuronal connectivity changes and reduced synaptic density. Strikingly, acute SD induces brain region– and subregion-specific changes in synaptic plasticity in adult mice, suggesting localized mechanisms of vulnerability. Microglia, the brain's immune cells, are important contributors to synaptic plasticity, and their functions are affected by various paradigms of acute SD. As a highly heterogeneous population, microglia exhibit functional differences between brain regions and environmental conditions. We thus aimed to determine compare two commonly used but experientially distinct SD paradigms, and explore possible differences in microglial properties across hippocampal subregions two 2 SD paradigms , hypothesizing that microglia contribute to the region-specific modulation of synaptic plasticity. We exposed adult male mice to 6 hours of SD through the paradigms of gentle handling or novelty exposure. We observed a decreased microglial density with novelty exposure compared to control and gentle handling in the CA1 SR , but not the CA3 SR . Microglial soma area, perimeter, and morphological index were reduced with novelty exposure in both the CA1 and CA3 SR . Microglial arborization circularity and solidity were also reduced, and microglial arborization perimeter increased after novelty exposure, but only in the CA1 SR . Moreover, we measured an increased number of microglia containing positive puncta for cluster of differentiation 68, a marker of phagolysosomal activity, after novelty exposure in the CA1 SR , without any effect observed in the CA3 SR . Lastly, using advanced scanning electron microscopy, we observed decreased microglial cytoplasm circularity and solidity, and an increased number of fully digested phagosomes within microglia following novelty exposure but not gentle handling and only in the CA1 SR . Overall, our results indicate that microglial features are altered by SD depending on the hippocampal region, specifically in the CA1, and more so in SD by novelty exposure, thereby reinforce that ‘it matters what keeps you awake at night’. Therefore, care should be taken concerning SD procedures as they can directly impact the conclusions. • Acute sleep deprivation impacts microglia differently by paradigm and region. • Microglial density was reduced with novelty exposure in the hippocampal CA1. • Microglial morphology was modified by novelty exposure in the CA1 and CA3. • Microglial phagolysosomal marker increased following novelty exposure. • At the nanoscale, microglial phagosomes differed with novelty exposure.
Kox et al. (Sun,) studied this question.