Central amygdala somatostatin neurons modulate stress-induced sleep-onset insomnia

Sleep-onset insomnia, characterized by difficulty falling asleep, is
linked to increased health risks. Previous studies have shown that the
central amygdala (CeA) plays a crucial role in stress regulation, with the
somatostatin neurons in the CeA (CeASST+) involved in adaptive stress
responses. However, the role of CeASST+ neurons in stress-induced
sleep-onset insomnia remains unclear. In this study, we found that the
activity of CeASST+ neurons is closely associated with stressful
events using fiber photometry in mice. Acute optogenetic activation of
CeASST+ neurons induced a rapid transition from non-rapid eye
movement (NREM) sleep to wakefulness. Semi-chronic optogenetic and
chemogenetic activation of CeASST+ neurons led to prolonged sleep-onset
latency and increased wakefulness. Chemogenetic inhibition of these
neurons ameliorated sleep-onset insomnia induced by stressful stimuli but
did not affect sleep-wake behavior under physiological conditions.
Collectively, our results suggested that CeASST+ neurons are a
key neural substrate for modulating stress-induced sleep-onset insomnia,
without influencing physiological sleep. These findings highlight CeASST+
neurons as a promising target for treating stress-related sleep-onset
insomnia in clinical practice.