A newly discovered neural pathway links emotional stimuli to wakefulness

Tsukuba, Japan—Emotional states and stress strongly influence sleep-wake regulation. The amygdala and its related structures have long been implicated in regulating arousal. However, the underlying neural mechanisms remain unclear.

In this study, the researchers examined how GABAergic neurons in the BNST interact with glutamatergic neurons in the DpMe to induce rapid arousal from non-rapid eye movement (NREM) sleep in mice. Optogenetic stimulation of BNST GABAergic neurons during NREM sleep resulted in immediate arousal, accompanied by a robust increase in DpMe neuronal activity. Conversely, selective ablation of glutamatergic neurons in the DpMe significantly reduced this response, demonstrating their essential role in the process.

This study was the first to thoroughly describe a BNST-DpMe neural pathway mediating emotional signals to arousal centers. In addition, the findings offer novel insights into how mental stressors such as fear and anxiety can disrupt sleep and highlights potential therapeutic targets for stress-related insomnia and mood disorders.

###
This study was supported by the World Premier International Research Center Initiative (WPI), a JSPS KAKENHI Grant-in-Aid for JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (JP 18H02595) (TS), Grant-in-Aid for Challenging Research (Exploratory) 21K19287(TS), JSPS KAKENHI Grant-in-Aid for Scientific Research (A) (JP 21H05036) (TS), JSPS KAKENHI Grant Number JP 23H04941 (TS), AMED Moonshot Research and Development Program, Grant Number JP21zf0127005 (TS), JSPS Fund for the Promotion of Joint International Research 22K213511(TS) and JST, CREST Grant Number JPMJCR24T4, JSPS Grant-in-Aid for Transformative Research Areas (A) 23H04941(TS).

_{Original Paper}

Title of original paper:
The bed nucleus of the stria terminalis- deep mesencephalic nucleus circuit linking emotion and wakefulness

Journal:
The Journal of Neuroscience

DOI:
10.1523/JNEUROSCI.1083-25.2025

_{Correspondence}

Professor SAKURAI, Takeshi
Assistant Professor Yoan Cherasse
Institute of Medicine / International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba

_{Related Link}

Tsukuba Institute for Advanced Research (TIAR)

International Institute for Integrative Sleep Medicine (WPI-IIIS)

Institute of Medicine

About the World Premier International Research Center Initiative (WPI)
The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

See the latest research news from the centers at the WPI News Portal: https://www.eurekalert.org/newsportal/WPI
Main WPI program site:  www.jsps.go.jp/english/e-toplevel

About International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba
World-class institute for sleep medicine, aiming to solve the mechanism of sleep/wakefulness by conducting basic to translational research
The mission of IIIS is to be a multidisciplinary, international hub for the research to elucidate the function of sleep and the fundamental mechanisms of sleep/wake regulation, to elucidate molecular pathogenesis of sleep disorders and related diseases, to develop preventive measures, diagnostic methods, and treatments for sleep.