Sleep decreases neuronal activity control of microglial dynamics in mice.

Microglia, the brain-resident immune cells, are highly ramified with dynamic processes transiently contacting synapses. These contacts have been reported to be activity-dependent, but this has not been thoroughly studied yet, especially in physiological conditions. Here we investigate neuron-microglia contacts and microglia morphodynamics in mice in an activity-dependent context such as the vigilance states. We report that microglial morphodynamics and microglia-spine contacts are regulated by spontaneous and evoked neuronal activity. We also found that sleep modulates microglial morphodynamics through Cx3cr1 signaling. At the synaptic level, microglial processes are attracted towards active spines during wake, and this relationship is hindered during sleep. Finally, microglial contact increases spine activity, mainly during NREM sleep. Altogether, these results indicate that microglial function at synapses is dependent on neuronal activity and the vigilance states, providing evidence that microglia could be important for synaptic homeostasis and plasticity.