Thirst reweights temperature preference through dual dopaminergic and endocrine modulation in Drosophila

Internal physiological states shape behavior by modulating sensory processing, yet the underlying neural mechanisms remain largely unresolved. Here, we demonstrate that thirst biases temperature preference in Drosophila melanogaster by enhancing hot avoidance while suppressing cold avoidance. Combining quantitative behavioral assays, in vivo calcium brain imaging, and targeted neural manipulations, we identify γ mushroom body neurons (γ MBns) as a key integrative node for thermal and internal state signals. We further reveal a dual neuromodulatory mechanism in which dopaminergic protocerebral anterior medial (PAM)-γ5 neurons and protocerebral posterior lateral (PPL1)-γ1pedc neurons oppositely regulate cold and hot representations through distinct receptors, Dop1R2 and DopEcR, respectively. In water-sated flies, cold stimuli activate PAM-γ5 neurons, whose dopamine release enhances cold-evoked responses in γ MBns via Dop1R2. In parallel, hot stimuli recruit PPL1-γ1pedc neurons, which engage the steroid hormone 20-hydroxyecdysone (20E)-mediated DopEcR-dependent mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) mechanism to suppress hot-evoked responses. Thirst attenuates both pathways, which results in a reweighting of thermal representations that biases behavioral choice toward cooler environments. Together, our findings uncover a circuit and molecular framework by which internal states dynamically reconfigure sensory representations to guide adaptive decision-making.