How Mice Reveal the Neurons that Cause Stress and Poor Sleep?

When confronted with a stressful day, many people experience disrupted sleep patterns, but the underlying mechanisms are not fully understood. Researchers have made a significant stride by identifying a group of neurons in mice brains responsible for regulating brief periods of wakefulness known as microarousals. This discovery holds promise in elucidating how stress impacts sleep, providing potential targets for more effective treatments of stress-related sleep impairments, according to Ketema Paul, a neuroscientist at the University of California, Los Angeles.

Microarousals are a natural component of sleep for both mice and humans, occurring alongside deep sleep phases called non-rapid eye movement (non-REM) sleep. However, an excessive frequency of microarousals can lead to fragmented and poor-quality sleep or contribute to sleep disorders like insomnia, as explained by study co-author Shinjae Chung, a neuroscientist at the University of Pennsylvania in Philadelphia.

Chung and her team sought to understand the brain circuits regulating microarousals and their connection to acute stress, which stems from sudden, significant events. To induce acute stress in mice, researchers subjected them to repeated attacks from an aggressive mouse. After removing the hostile mouse, the targeted animal continued to experience the effects of social defeat stress, impacting its sleep as it transitioned into the sleep state.

Focusing on the hypothalamus

The researchers utilized electroencephalography and electromyography (EEG and EMG) to monitor the sleep-wake states of stressed mice and employed fibre photometry, a type of brain imaging, to observe the firing patterns of specific neuron populations during sleep. Focusing on the preoptic area of the hypothalamus, a region known for its role in sleep regulation, the scientists targeted various cell groups within this almond-sized structure.

Stressed mice, having undergone repeated aggressive encounters, exhibited an increased frequency of microarousals and spent less time in non-REM sleep compared to their baseline state. The researchers identified a subpopulation of cells, specifically glutamatergic neurons, in the preoptic area that were activated during normal rhythmic microarousals in non-REM sleep. Following acute stress, these same neurons showed heightened activity during sleep. When the researchers inhibited the glutamatergic neurons, stressed mice slept for longer intervals between microarousals, indicating the importance of these neurons in regulating sleep stability and preventing fragmentation. Shinjae Chung emphasizes the significance of these neurons in maintaining sleep continuity and stability.

Stress and sleep

The recent findings, indicating that acute stress leads to more wakefulness and fewer periods of deep sleep in mice, diverge from some previous studies suggesting that stress can result in increased sleep in rodents, notes Brittany Bush, a sleep scientist at Stanford University. She emphasizes the importance of considering various factors that could contribute to these differing results. One key distinction lies in the environment where the mice fell asleep — the current study had them sleep in the same environment where the acute stress occurred, unlike previous studies where mice returned to their home cages. Shinjae Chung highlights the potential impact of individual differences in mice resilience to stress and suggests that future research could explore these variations.

While the immediate application of these findings to human sleep disorders is unlikely, they contribute to a deeper understanding of the complex relationship between sleep and stress. Ketema Paul sees the identification of a specific circuit involved in regulating sleep as a crucial step, offering the potential to address broader questions about the interplay between human sleep, stress, and their diverse effects on health in future research.

Resources

1. ^JOURNAL Coleman, J. (2023). Neurons responsible for poor sleep and stress found in mice. Nature. [Nature]
2. ^JOURNAL Smith, J., Honig-Frand, A., Antila, H., Choi, A., Kim, H., Beier, K. T., Weber, F., & Chung, S. (2023). Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons. Current Biology. [Current Biology]

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