THE ORCHESTRA OF SLEEP: DRD1-EXPRESSING NEURONS IN THE CENTRAL CLOCK AS THE CONDUCTOR OF SLEEP AND AUTONOMIC BALANCE IN RATS

Sleep, despite being highly conserved across mammalian species, has mechanisms that remain unknown, and its disruptions are linked to many diseases. One of the most common manifestations of sleep disorders is sleep fragmentation, which bidirectionally correlates with metabolic and cardiovascular diseases due to autonomic imbalance. However, what regulates the homeostasis of sleep and autonomic balance remains unanswered. One proposed regulator are the dopamine receptor D1 (Drd1)-expressing neurons in the suprachiasmatic nucleus (SCN), which have long been considered nonessential in adult circadian rhythms. We aim to determine how altering Drd1-SCN neuron activity affects sleep architecture and autonomic balance in rats fed either a standard or free-choice high-fat high-sugar (fcHFHS) diet. We will utilize DREADD-based chemogenetics to stimulate Drd1-SCN neurons in adult Drd1-Cre transgenic male rats. The 24-hour sleep architecture will be measured using locomotor activity detected by infrared beams in home cages. To measure autonomic balance, we will immunofluorescently detect c-Fos expression in the paraventricular nucleus (PVN) of the hypothalamus and the dorsal motor nucleus of the vagus (DMV), where pre-autonomic and parasympathetic preganglionic neurons are located, respectively. We expect that stimulation of Drd1-SCN neurons will increase sleep fragmentation, with the fcHFHS diet exacerbating this effect. The neuronal activity of pre-autonomic neurons in the PVN is expected to increase following stimulation, while parasympathetic DMV neuronal activity may show slight changes or a decrease. The fcHFHS diet is expected to enhance these effects. By demonstrating that Drd1-SCN neurons affect sleep and autonomic balance, opportunities for preventive and therapeutic strategies may be opened.