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A Neural Circuit Mechanism Integrating Motivational State with Memory Expression in Drosophila Michael J. Krashes,1,4,5 Shamik DasGupta,1,5 Andrew Vreede,2 Benjamin White,2 J. Douglas Armstrong,3 and Scott Waddell1,* 1Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA 2Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA 3Institute for Adaptive and Neural Computation, School of Informatics, 5 Forrest Hill, University of Edinburgh, Edinburgh EH1 2QL, UK 4Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA 5These authors contributed equally to this work *Correspondence: scott.waddell@ DOI 10.1016/j.cell.2009.08.035SUMMARY Behavioral expression of food-associated memory in fruit flies is constrained by satiety and promoted by hunger, suggesting an influence of motivational state. Here, we identify a neural mechanism that integrates the internal state of hunger and appetitive memory. We show that stimulation of neurons that express neuropeptide F (dNPF), an ortholog of mammalian NPY, mimics food deprivation and pro- motes memory performance in satiated flies. Robust appetitive memory performance requires the dNPF receptor in six dopaminergic neurons that innervate a distinct region of the mushroom bodies. Blocking these dopaminergic neurons releases memory per- formance in satiated flies, whereas stimulation suppresses memory performance in hungry flies. Therefore, dNPF and dopamine provide a motiva- tional switch in the mushroom body that controls the output of appetitive memory. INTRODUCTION Motivation provides behavior with purpose and intensity and ensures that particular motor actions are expressed at the appropriate time. Although the concept of motivation has inter- ested psychologists and ethologists for decades (Hull, 1951; Tolman,