Neuronal mechanisms of sleep alterations in Parkinson's Disease: A circuit based investigation

点击翻译按钮获取中文摘要

Among the well-established non-motor symptoms of Parkinson disease (PD), compulsive eating stands among the most frequent impulse control disorder. This disorder is attributed to dopamine (DA) dysfunction following both dopaminergic neurodegeneration and chronic DA replacement therapy in PD patients. Recent evidence highlighted the causal impact of sleep alterations in precipitating metabolic and food-seeking behavioral disorders. Building on these findings, we have recently revealed the crucial importance of the medial prefrontal cortex (mPFC) in linking sleep quality with food preference and energy consumption. The mPFC is a frontal neuronal hub that is crucial for executive functions. Given that midbrain DA neurons have dense projections to the mPFC, we aimed in this project to elucidate the precise role of DA neurotransmission in mediating food preference based on their nutritional and metabolic impact. To interfere with DA neurotransmission, we employed chemogenetic to selectively inhibit DA neurons in the ventral tegmental area (VTA).After habituation into our behavioral settings, animals were given free access to highly palatable food (Chocolate and cheese) and standard laboratory chow. Food preference and intake was monitored daily under both baseline 12h/12h light/dark (LD) cycle and following 6h sleep deprivation. Under LD conditions, control animals showed high preference for palatable fatty items (cheese) over carbohydrate-rich food (chocolate and standard chow). After inhibition of DA neurons, animals still show a preference for fatty food over sweet food.