Microglia protect memories formed during sleep deprivation

Purpose: To determine the specific effects of 6 hours sleep deprivation after a learning event on the transcriptomes of microglia. Sleep deprivation can generate inflammatory responses in the neuronal environment. In turn, this inflammation increases sleep drive, leading to a rebound in sleep duration. Microglia, a type of support cell found exclusively in the brain, have previously been found to release of inflammatory signals and exhibit altered characteristics in response to sleep deprivation. Together, this suggests microglia may be partially responsible for the brain’s response to sleep deprivation through their inflammatory activity. In this study, we fully and selectively ablated microglia from the mouse brain and assessed resulting sleep, circadian, and sleep deprivation phenotypes. We find 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 synapses and associated memories formed during a period of sleep deprivation, further expanding the list of known functions for microglia in synaptic modulation. Mice were fear conditioned and then sleep deprived for 6 hours for sample extraction. Control mice were fear conditioned and allowed to sleep for 6 hours following training. All samples were extracted from hippocampal dissections using a microglia-specific ribotag IP pulldown method. Mouse line: P2RY12CreER x Rpl22HA RiboTag. Two biological replicates were pooled for each technical replicate to ensure enough sample for sequencing.