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 analogue 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, making it more responsive to an odor cue previously paired with ethanol. A combination of genetic and connectome analyses revealed that 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. ### Competing Interest Statement The authors have declared no competing interest. National Institute on Alcohol Abuse and Alcoholism, R01AA024434 National Institute of Neurological Disorders and Stroke, F99NS118741 National Institute of General Medical Sciences, R01GM115510 National Institute on Deafness and Other Communication Disorders, R01DC017146, R01DC020703 Howard Hughes Medical Institute, https://ror.org/006w34k90, Gilliam award to K.M.N. Hubert & Richard Hanlon Trust Carney Institute for Brain Science at Brown University, Innovation Award to G.B.