Sleep-wake states are encoded across emotion-regulation regions of the mouse brain.

Abstract

Emotional dysregulation is highly comorbid with sleep disturbances. Sleep is comprised of unique physiological states that are reflected by conserved brain oscillations. Though the role of these state-dependent oscillations in cognitive function has been well-established, less is known regarding the nature of state-dependent oscillations across brain regions that strongly contribute to emotional function. To characterize these dynamics, we recorded local field potentials simultaneously from multiple cortical and subcortical regions implicated in sleep and emotion-regulation and characterized widespread patterns of spectral power and synchrony between brain regions during sleep-wake states in male and female mice. First, we showed that single brain regions encode sleep state, albeit to various degrees of accuracy. We then identified network-based classifiers of sleep based on the combination of features from all recorded brain regions. Spectral power and synchrony from brain networks allowed for automatic, accurate and rapid discrimination of wake, non-REM sleep (NREM) and rapid eye movement (REM) sleep. When we examined the impact of commonly prescribed sleep-promoting medications on neural dynamics across these regions, we found disparate alterations to both cortical and subcortical activity across all three states. Finally, we found that a stress manipulation that disrupts circadian rhythm in male mice increased sleep fragmentation without altering the underlying average brain dynamics across sleep-wake states. Thus, we characterized state-dependent brain dynamics across regions canonically associated with emotions.Significance Statement Sleep and emotion regulation are known to be intertwined at the level of behavior and in neuropsychiatric illnesses. Here, we examined how brain regions involved in emotion regulation encode wake and sleep states by performing multi-site electrophysiological recordings in mice. We developed classifiers that rapidly labeled sleep-wake states from brain activity alone. We then identified how commonly prescribed sleep-inducing medications have unique impacts on brain activity throughout these emotion-regulation regions. Finally, we explored the impact of circadian rhythm disruption on sleep architecture and brain activity. Together, these data shed light on how brain regions that regulate emotion behave during sleep so that one day, treatments to improve both sleep and emotional well-being may be developed.