Sleep-related respiratory disruptions and laterodorsal tegmental nucleus in a mouse model of Parkinson’s disease

Parkinson’s disease (PD) is a chronic neurodegenerative disorder affecting the motor system, with non-classic symptoms such as sleep disturbances and respiratory dysfunctions. These issues reflect a complex pathophysiological interaction that severely impacts quality of life. Using a 6-hydroxydopamine (6-OHDA) mouse model of PD, we investigated these connections by analyzing sleep patterns and respiratory parameters during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Our findings revealed altered breathing, including reduced respiratory frequency and increased apneas during both NREM and REM. To address these abnormalities, we employed chemogenetic stimulation of cholinergic neurons in the laterodorsal tegmental nucleus (LDTg), a key region for sleep-wake regulation and respiratory modulation. This intervention normalized respiratory function. These results highlight the critical role of LDTg cholinergic neurons in the coordinating sleep and breathing, suggesting that targeting these neurons could offer a therapeutic strategy for managing PD-related respiratory complications. [Display omitted] •Sleep and respiratory changes are linked with neurodegeneration in the 6-OHDA model•6-OHDA reduces respiratory frequency, apneas in sleep, and LDTg cholinergic neurons•LDTg cholinergic neurons regulate respiratory frequency/apneas in sleep-wake cycles•Modulating LDTg neurons may help manage respiratory complications in PD Disease; Biological sciences; Neuroscience