Brainstem circuit for sickness-induced sleep

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.