Oscillatory Population-Level Activity of Dorsal Raphe Serotonergic Neurons Is Inscribed in Sleep Structure

Area of Science:

• Neuroscience
• Sleep Science
• Neurophysiology

Background:

• Single-unit activity of dorsal raphe (DR) serotonin (5-HT) neurons is well-characterized across sleep-wake states.
• Population-level activity of DR 5-HT neurons and their role in brain-wide regulation remain largely unknown.
• Understanding DR 5-HT neuron population dynamics is crucial for deciphering sleep-wake transition mechanisms.

Purpose of the Study:

• To investigate the population-level activity patterns of DR 5-HT neurons throughout the sleep-wake cycle in mice.
• To explore the relationship between DR 5-HT neuron population activity and electroencephalogram (EEG) fluctuations.
• To determine the causal role of DR 5-HT neuron activity in regulating sleep-wake states.

Main Methods:

• Ratiometric fiber photometry was employed to measure population Ca2+ signals of DR 5-HT neurons in male and female mice.
• Sleep-wake states were monitored alongside DR 5-HT neuron activity.
• Optogenetic and pharmacological manipulations were used to alter 5-HT neuron activity during sleep.

Main Results:

• DR 5-HT neuron population activity exhibited slow oscillations during NREM sleep, with troughs increasing across sleep progression.
• REM sleep initiation was associated with a minimum trough in 5-HT activity.
• Oscillatory 5-HT activity showed unique coupling with wideband EEG power fluctuations; optogenetic/pharmacological silencing revealed its association with EEG fluctuations.

Conclusions:

• NREM sleep is not a monotonous state but exhibits dynamic changes linked to oscillatory DR 5-HT neuron population activity.
• DR 5-HT neuron population activity plays a causal role in triggering wakefulness and influencing sleep state transitions.
• The findings suggest that NREM sleep comprises at least binary states, evidenced by oscillatory 5-HT activity and EEG fluctuations.