Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons 2023 Smith et al

Highlights

• POA glutamatergic neurons become activated during microarousals in NREM sleep
• Stress activates POA glutamatergic neurons, leading to fragmented sleep
• Inhibiting POA glutamatergic neurons attenuates stress-induced sleep fragmentation
• Presynaptic inputs in the lateral hypothalamus become activated after stress

Summary

Sleep disturbances are detrimental to 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 in mice, we examine the activity of genetically defined POA subpopulations during sleep.

We find 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 promotes MAs and wakefulness. Exposure to acute social defeat stress fragments NREMs and significantly increases the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. By reducing MAs, optogenetic inhibition during spontaneous sleep and after stress consolidates NREMs. Monosynaptically restricted rabies tracing reveals that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. In particular, presynaptic glutamatergic neurons in the lateral hypothalamus become activated after stress, and stimulating their projections to the POA promotes MAs and wakefulness. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.

Paywall, https://www.cell.com/current-biology/fulltext/S0960-9822(23)01585-3

 

Neurons responsible for poor sleep and stress found in mice

"Researchers have now identified a group of neurons in the brains of mice that are involved in regulating blips of wakefulness, called microarousals. The finding1 could help to explain how stress disrupts sleep, says Ketema Paul, a neuroscientist at the University of California, Los Angeles. “That is a very big step in the right direction as we look for targets to better treat sleep impairments that result from stress.”

Microarousals are a normal part of sleep for mice and humans. Throughout the course of a night’s rest, periods of brief waking are mixed in with stretches of deep sleep called non-rapid eye movement (non-REM) sleep. But when microarousals happen more frequently than normal, they lead to fragmented, poor-quality sleep or even sleep disorders such as insomnia, says study co-author Shinjae Chung, a neuroscientist at the University of Pennsylvania in Philadelphia."

"The researchers found that a subpopulation of cells in the preoptic area of the hypothalamus were activated in non-REM sleep during normal, rhythmic micro-arousals — and that the same neurons, called glutamatergic neurons, were more active during sleep after acute stress. The researchers also experimented with inhibiting the glutamatergic neurons; when the neurons were switched off, the opposite effect happened and stressed mice slept for longer between microarousals. This is probably one of many pathways that help to regulate sleep quality, the team reports in Current Biology.

“These neurons are really important for regulating sleep stability, for sleep continuity, so that your sleep is not fragmented,” Chung says."

https://www.nature.com/articles/d41586-023-03936-0

 

Since many ME theories involve the hypothalamus, these findings might help explain our sleep problems.