Hunger recruits a parallel circuit encoding alcohol reward.

Internal states like hunger, pain, thirst, and arousal can bias behavior by affecting sensory and memory processing. Internal states are critical to understand in the context of alcohol addiction because they influence cravings, reinstatement, and relapse. Norepinephrine plays a key role in both hunger and alcohol-induced arousal and preference, but the circuit-level mechanisms through which it modulates the influence of hunger on alcohol preference are not well understood. We sought to address this using intersectional genetic tools for manipulating neurons expressing octopamine, the invertebrate analog of vertebrate norepinephrine. We identified a single octopamine neuron required for ethanol seeking only when Drosophila are food deprived. Hunger increased baseline activity in this neuron, thus making it more responsive to an odor cue previously paired with ethanol. A combination of genetic and connectome analyses revealed that the synaptic partners of this octopaminergic neuron form a functional module that acts on Drosophila memory circuitry. Thus, we show that hunger recruits a parallel circuit that drives learned ethanol preference, providing a neuronal framework through which internal state influences the expression of memory for ethanol-associated cues. VIDEO ABSTRACT.