Local Drd1-neurons input to subgroups of arcuate AgRP/NPY-neurons

Obesity is a pandemic afflicting more than 300 million people worldwide, driven by consumption of calorically dense and highly rewarding foods. Dopamine (DA) signaling has been implicated in neural responses to highly palatable nutrients, but the exact mechanisms through which DA modulates homeostatic feeding circuits remains unknown. A subpopulation of arcuate (ARC) agouti-related peptide (AgRP)/neuropeptide Y (NPY) (ARC(AgRP/NPY+)) neurons express the D(1A) dopamine receptor (Drd1) and are stimulated by DA, suggesting one potential avenue for dopaminergic regulation of food intake. Using patch clamp electrophysiology, we evaluated the responses of ARC Drd1-expressing (ARC(Drd1+)) neurons to overnight fasting and leptin. Collectively, ARC(Drd1+) neurons were less responsive to caloric deficit than ARC(AgRP/NPY+) neurons; however, ARC(Drd1+) neurons were inhibited by the satiety hormone leptin. Using Channelrhodopsin-2-Assisted Circuit Mapping, we identified novel subgroups of ARC(Drd1+) neurons that inhibit or excite ARC(AgRP/NPY+) neurons. These findings suggest dopamine receptive neurons have multimodal actions in food intake circuits.