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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
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Brainstem circuit for sickness-induced sleep.

Dana Darmohray1, Jiao Sima1, Chien-Hao Chen1

  • 1Department of Neuroscience, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.

Science Advances
|December 10, 2025
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Summary
This summary is machine-generated.

Immune activation triggers sleep to aid illness recovery. Researchers discovered a brainstem circuit, starting in the nucleus of the solitary tract (NST), that promotes non-rapid eye movement (NREM) sleep during sickness.

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Area of Science:

  • Neuroscience
  • Immunology
  • Sleep Science

Background:

  • Sickness-induced sleep aids recovery but its neural basis is unclear.
  • Understanding the brain mechanisms of sickness sleep is crucial for treating illnesses.

Purpose of the Study:

  • To identify the neural circuits in the brainstem responsible for sickness-induced non-rapid eye movement (NREM) sleep.
  • To investigate the role of the nucleus of the solitary tract (NST) and parabrachial nucleus (PB) in regulating sleep during immune activation.

Main Methods:

  • Used activity-dependent genetic labeling to identify NST neurons activated by lipopolysaccharide (LPS).
  • Employed chemogenetics to activate these NST neurons and assess their effect on NREM sleep.
  • Performed fiber photometry to measure neuromodulator release (e.g., norepinephrine) from the locus coeruleus.

Main Results:

  • Activation of LPS-sensitive NST neurons strongly promoted NREM sleep.
  • These NST neurons project to the PB, where activated neurons also promote NREM sleep.
  • Sickness stimuli or activation of NST/PB neurons reduced norepinephrine release from the locus coeruleus.

Conclusions:

  • A brainstem circuit involving the NST and PB mediates sickness-induced NREM sleep.
  • This circuit regulates sleep by modulating the release of wake-promoting neuromodulators like norepinephrine.
  • Findings provide insight into the neural regulation of sleep during immune responses.