INTEGRATION OF MULTIMODAL NEURAL RECORDINGS DURING CLOSED-LOOP AUDITORY STIMULATION OF SLOW-WAVE SLEEP IN A NEURODEGENERATIVE MODEL

Sleep disturbances are common during the prodromal phase of Parkinson’s disease (PD), with slow-wave sleep (SWS) being particularly affected. Given the essential restorative role of SWS, its impairment may represent early neurodegenerative changes and could also contribute to disease progression. Closed-loop auditory stimulation (mCLAS) targeting slow waves has been shown to deepen SWS and improve sleep-wake cycle alterations in PD murine models. However, the neural circuits involved in this intervention need to be elucidated. This study aims to investigate the brain activity patterns associated with mCLAS during SWS in a PD mouse model, with a particular focus on corticothalamic circuits. We expanded the already established EEG/EMG-based mCLAS framework by integrating local field potentials and multi-unit activity recordings. The recordings target key nodes of the corticothalamic network involved in sleep and auditory modulation, including the thalamic reticular nucleus, the ventral posteromedial nucleus, and the auditory cortex. Ex vivo whole-brain mapping of immediate-early gene expression will be implemented using tissue clearing technique and 3D imaging to assess cellular activation associated with stimulation. We established and optimized the experimental protocol, encompassing surgical procedures, evaluation of different probe types, precise probe placement in regions of interest in mice of different genotypes and sexes, and complete system synchronization. The next steps involve electrophysiological recordings, followed by data analysis to assess neural activity during sleep-wake states and stimulation phases. This work is expected to elucidate the mechanisms underlying mCLAS and guide the advancement of oscillotherapy-based neurotechnologies for neurodegenerative disorders in patients.