State-dependent remodeling of dopamine receptor expression across mushroom body in Drosophila

Internal physiological states profoundly reshape sensory processing and whether distinct internal state modulate the expression of neurotransmitter receptors. Here, using endogenous split-GFP receptor tagging in Drosophila, we systematically mapped dopamine receptor dynamics across all 15 mushroom body (MB) lobe compartments under hunger and thirst states. We found that hunger selectively increased Dop1R1 expression throughout αβ MB lobe compartments and increased Dop2R expression across α'β' MB lobe compartments. In contrast, thirst broadly upregulated both Dop1R1 and Dop2R in γ MB lobe compartments while simultaneously reducing Dop2R expression in αβ MB lobe. Thirst also induced compartment-specific remodeling within α'β' MB neurons (MBn), including increased Dop1R1 expression in α'3 and decreased expression in β'1 regions. Notably, these receptor dynamics occurred without significant changes in baseline dopamine release from upstream dopaminergic neurons (DAN) during different internal physiological states, suggesting that hunger and thirst states regulate downstream circuit responsiveness primarily through selective remodeling of dopamine receptor expression rather than alterations in presynaptic dopaminergic activity. Together, our findings uncover a previously unrecognized mechanism by which internal physiological states reshape dopaminergic receptor organization to regulate neural circuit functions.