Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding.
The nervous system evolved to coordinate flexible goal-directed behaviors by integrating interoceptive and sensory information. Hypothalamic Agrp neurons are known to be crucial for feeding behavior. Here, however, we show that these neurons also orchestrate other complex behaviors in adult mice. Activation of Agrp neurons in the absence of food triggers foraging and repetitive behaviors, which are reverted by food consumption. These stereotypic behaviors that are triggered by Agrp neurons are coupled with decreased anxiety. NPY5 receptor signaling is necessary to mediate the repetitive behaviors after Agrp neuron activation while having minor effects on feeding. Thus, we have unmasked a functional role for Agrp neurons in controlling repetitive behaviors mediated, at least in part, by neuropeptidergic signaling. The findings reveal a new set of behaviors coupled to the energy homeostasis circuit and suggest potential therapeutic avenues for diseases with stereotypic behaviors.
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Graduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil. Electronic address: marcelo.dietrich@yale.edu.
Marcelo O
MO
Dietrich
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Graduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil.
Marcelo R
MR
Zimmer
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Jeremy
J
Bober
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Kavli Institute for Neuroscience at Yale University, New Haven, CT 06520, USA.
Tamas L
TL
Horvath
D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000008:administration & dosage; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000008:administration & dosage; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000145:classification / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D018756:GABA Antagonists; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin