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Researchers at University of Tsukuba have identified a previously uncharacterized neural circuit that directly links emotional processing to arousal. In the pathway, GABAergic neurons in the bed nucleus of the stria terminalis (BNST)—part of the extended amygdala—promote wakefulness by activating glutamatergic neurons in the deep mesencephalic nucleus (DpMe) of the midbrain. This circuit may be a key mechanism underlying stress-induced sleep disturbances.

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.

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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