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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia are involved in the protection of memories formed during sleep deprivation
Nicholas W Gentry1, Thomas McMahon1, Maya Yamazaki1
1Department of Neurology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Abstract:
Sleep deprivation can generate inflammatory responses in the central nervous system. In turn, this inflammation increases sleep drive, leading to a rebound in sleep duration. Microglia, the innate immune cells found exclusively in the CNS, have previously been found to release inflammatory signals and exhibit altered characteristics in response to sleep deprivation. Together, this suggests that microglia may be partially responsible for the brain's response to sleep deprivation through their inflammatory activity. In this study, we ablated microglia from the mouse brain and assessed resulting sleep, circadian, and sleep deprivation phenotypes. We find that microglia are dispensable for both homeostatic sleep and circadian function and the sleep rebound response to sleep deprivation. However, we uncover a phenomenon by which microglia appear to be essential for the protection of fear-conditioning memories formed during the recovery sleep period following a period of sleep deprivation. This phenomenon occurs potentially through the upregulation of synaptic-homeostasis related genes to protect nascent dendritic spines that may be otherwise removed or downscaled during recovery sleep. These findings further expand the list of known functions for microglia in synaptic modulation.
Insights
Microglia, the brain's immune cells, are not essential for sleep regulation or recovery sleep. However, they play a crucial role in protecting fear memories formed during sleep after sleep deprivation.
Area of Science:
- Neuroscience
- Immunology
- Sleep Science
Background:
- Sleep deprivation induces central nervous system inflammation, increasing sleep drive and rebound sleep.
- Microglia, CNS-resident immune cells, release inflammatory signals and change in response to sleep loss, suggesting a role in the brain's response to sleep deprivation.
Purpose of the Study:
- To investigate the role of microglia in sleep, circadian rhythms, and responses to sleep deprivation.
- To determine if microglia are essential for sleep rebound and the protection of memories formed during recovery sleep.
Main Methods:
- Microglia were ablated in the mouse brain.
- Sleep, circadian phenotypes, and sleep deprivation responses were assessed.
- The impact on fear-conditioning memory consolidation during recovery sleep was evaluated.
Main Results:
- Microglia ablation did not affect homeostatic sleep, circadian function, or the sleep rebound response.
- Microglia were found to be essential for protecting fear-conditioning memories consolidated during recovery sleep following sleep deprivation.
- This protective effect may involve the upregulation of genes related to synaptic homeostasis, preserving dendritic spines.
Conclusions:
- Microglia are dispensable for basic sleep regulation and the immediate response to sleep deprivation.
- Microglia play a critical, previously unrecognized role in memory consolidation during recovery sleep by modulating synaptic plasticity.
- These findings highlight novel functions of microglia in synaptic modulation and memory.
