NEURAL CIRCUITS AND DYNAMICS REGULATING RAPID EYE MOVEMENT SLEEP

Rapid eye movement (REM) sleep is characterized by cortical activation, muscle atonia, and phasic events such as rapid eye movements and accelerated hippocampal theta oscillations. While REM sleep is known to be generated in the brainstem, the neural dynamics driving transitions to REM sleep and the potential involvement of cortical regions in its regulation remain poorly understood. This dissertation aims to elucidate the brain-wide control of REM sleep, from cortical areas to brainstem regions, and to understand how these neural populations coordinate to regulate this state. To investigate cortical regulation of REM sleep, we used optogenetic manipulations and pupillometry in mice, demonstrating that excitatory neurons in the medial prefrontal cortex (mPFC) promote REM sleep through projections to the lateral hypothalamus and regulate phasic events. Calcium imaging reveals that the majority of lateral hypothalamus-projecting mPFC neurons are maximally activated during REM sleep, with a subpopulation recruited during phasic theta accelerations. To explore brainstem dynamics regulating REM sleep, we combined Neuropixels recordings with dimensionality reduction. This revealed that population activity in midbrain and pons is dominated by two common components, one capturing strong infraslow fluctuations in neural activity. During NREM-to-REM transitions, population activity followed a stereotypic trajectory, preceded by an increase in the infraslow component. Single neuron analysis showed subpopulations of REM sleep-activated and -inhibited neurons across all areas, exhibiting opposing infraslow dynamics and diverging ramping activity between REM sleep episodes. Optogenetic activation of upstream REM sleep-promoting neurons in the medulla rapidly increased the infraslow component, facilitating NREM-to-REM transitions. Collectively, this work provides a comprehensive view of REM sleep regulation, from cortical influence to brainstem dynamics. It offers a quantitative framework for understanding population-level activity patterns governing REM sleep transitions and suggests that these dynamics are widely shared across brain areas.