How bright-light treatment improves sleep in stressed mice

Chronic stress is associated with sleep disturbance. In their new study, Lu Huang and colleagues identify the neural pathway behind this behavior, and at the same time, explain how bright-light treatment is able to counter it. The research was conducted in mice at Jinan University in China and published September 7^th in the open access journal PLOS Biology.

Bright-light treatment is known to improve sleep in those with sleep disorders, but how it works – and whether it works in cases of stress-induced sleep disturbances – was unknown. The researchers hypothesized that a part of the brain called the lateral habenula is deeply involved in this phenomenon because it both receives light signals from the eyes and can influence other parts of the brain that regulate sleep. To test this theory and fully characterize the neural pathway, the team performed a series of chemogenetic and optogenetic studies in a mouse model of chronic stress, which also showed irregular sleep. Specifically, chronic stress led to higher-than-normal amounts of non-REM sleep, which could be eliminated with bright-light treatment.

As hypothesized, the lateral habenula influenced the effects of stress on sleep. Its chemogenetic inhibition in stressed mice prevented the unusual high amounts of non-REM sleep, and on the flip side, its chronic activation in un-stressed mice resulted in extra non-REM sleep. Next, by separately activating habenular neurons that send signals to different regions of the brain, the researchers were able to identify the connection between the habenula and the rostromedial tegmental nucleus (RMT) as critical. Activating only these neurons mimicked the effects of stress on sleep, while inhibiting them in stressed mice mimicked the effects of bright-light treatment.

Lastly, the researchers showed that light-sensitive neurons in the lateral geniculate nucleus (LGN) naturally inhibit the habenula-RMT neurons, which explains why bright-light treatment can reduce stress-induced abnormalities in non-REM sleep. Understanding how bright-light treatment works can help devise optimal light treatments and perhaps pharmacological interventions targeting this pathway.

Coauthor Chaoran Ren adds, “A circuit mechanism has been identified that explains the effects of bright light treatment on sleep disruptions induced by chronic stress in mice.”

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In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002282  

Citation: Huang L, Chen X, Tao Q, Wang X, Huang X, Fu Y, et al. (2023) Bright light treatment counteracts stress-induced sleep alterations in mice, via a visual circuit related to the rostromedial tegmental nucleus. PLoS Biol 21(8): e3002282. https://doi.org/10.1371/journal.pbio.3002282

Author Countries: China

Funding: This work was supported by STI2030-Major Projects (https://www.most.gov.cn/index.html) (2021ZD0203100 to CRR), National Natural Science Foundation of China (https://www.nsfc.gov.cn) (31922030, 32171010 and 31771170 to CRR; 32171009 to LH; 81870823 to XRS), Guangdong Basic and Applied Basic Research Foundation (http://gdstc.gd.gov.cn) (2023B1515040010 to CRR; 2021B1515020035 to LH), Science and Technology Program of Guangdong (http://gdstc.gd.gov.cn) (2018B030334001 to CRR), Science and Technology Program of Guangzhou (http://kjj.gz.gov.cn) (202007030012 to CRR), Young Elite Scientist Sponsorship Program By CAST (https://www.cast.org.cn) (YESS20210181 to LH), Guangzhou Health Science and technology project (http://wjw.gz.gov.cn) (202102010325 to XC), Programme of Introducing Talents of Discipline to Universities (http://www.moe.gov.cn) (B14036 to FKS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.