Drd1 in the SCN and ARC: Findings from Patch Clamp Electrophysiology Studies of the Hypothalamus

The hypothalamus integrates sensory and peripheral signals to maintain essential homeostatic functions throughout the body. With respect to sleep and wakefulness, the suprachiasmatic nucleus (SCN) acts as the body’s primary central clock and manages the timing of essential behavior and physiological processes. With respect to appetite and food intake, the arcuate nucleus (ARC) acts as the primary mediator of homeostatic feeding, driving food intake behaviors when energy balance is low. Hypothalamic circuits controlling sleep and food intake in mammals are some of the most ancient structures in the mammalian nervous system, however the processes that maintain equilibrium in the wild have not been selected for in the context of modern life. In particular, we lack an understanding of how hedonic processes, such as those regulated by dopamine (DA) and reward systems, impinge on the healthy functioning of hypothalamic circuits in disease. Globally, human diets are increasingly composed of foods rich in fats and sugars, and consumption of these foods results in DA signaling in the midbrain and other regions. Identifying how DA acts on hypothalamic circuits is essential to combating the negative impacts that obesity and circadian dysregulation have on humanity. Here, I investigate the circuitry and signaling in these nuclei relevant to DA and the dopamine 1 receptor (Drd1). My work demonstrates that Drd1 neurons have multimodal and complex actions in hypothalamic nuclei, and modulate important neuronal populations vital to homeostatic processes.