Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons

Abstract

Sleep disturbances are detrimental for our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals, MAs) resulting in sleep fragmentation. The preoptic area of the hypothalamus (POA) is crucial for sleep control. However, how POA neurons contribute to the regulation of MAs and thereby impact sleep quality is unknown. Using fiber photometry recordings in mice, we examined the activity changes of genetically defined POA subpopulations during sleep. We found that POA glutamatergic neurons are rhythmically activated in synchrony with an infraslow rhythm in the spindle band of the electroencephalogram during non-rapid eye movement sleep (NREMs) and are transiently activated during MAs. Optogenetic stimulation of these neurons strongly promotes MAs. Exposure to acute social defeat stress significantly increased the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. Optogenetic inhibition during spontaneous sleep and after stress reduced MAs during NREMs and consequently consolidated sleep. Monosynaptically-restricted rabies tracing revealed that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.