Hunger-Driven Motivational State Competition.
Behavioral choice is ubiquitous in the animal kingdom and is central to goal-oriented behavior. Hypothalamic Agouti-related peptide (AgRP) neurons are critical regulators of appetite. Hungry animals, bombarded by multiple sensory stimuli, are known to modify their behavior during times of caloric need, rapidly adapting to a consistently changing environment. Utilizing ARCAgRPneurons as an entry point, we analyzed the hierarchical position of hunger related to rival drive states. Employing a battery of behavioral assays, we found that hunger significantly increases its capacity to suppress competing motivational systems, such as thirst, anxiety-related behavior, innate fear, and social interactions, often only when food is accessible. Furthermore, real-time monitoring of ARCAgRPactivity revealed time-locked responses to conspecific investigation in addition to food presentation, further establishing that, even at the level of ARCAgRPneurons, choices are remarkably flexible computations, integrating internal state, external factors, and anticipated yield. VIDEO ABSTRACT.
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA; Brown University Graduate Partnerships Program, Providence, RI 02912, USA.
C Joseph
CJ
Burnett
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA.
Chia
C
Li
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA.
Emily
E
Webber
Max Plank Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Gleueler Str. 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Str. 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; National Center for Diabetes Research (DZD), Ingolstädter Land Str. 1, 85764 Neuherberg, Germany.
Eva
E
Tsaousidou
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA.
Stephen Y
SY
Xue
Max Plank Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Gleueler Str. 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Str. 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; National Center for Diabetes Research (DZD), Ingolstädter Land Str. 1, 85764 Neuherberg, Germany.
Jens C
JC
Brüning
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: michael.krashes@nih.gov.
Michael J
MJ
Krashes
D054369:Agouti-Related Protein / Q000235:genetics / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D003463:Cues; D004435:Eating / Q000502:physiology; D006815:Hunger / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009042:Motivation / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000502:physiology
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse
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