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Cell. 2015 Mar 12;160(6):1222-32. doi: 10.1016/j.cell.2015.02.024. Epub 2015 Mar 5.

Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding.

Author information

1
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.
2
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.
3
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
4
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.

Abstract

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.

PMID:
25748653
PMCID:
PMC4484787
DOI:
10.1016/j.cell.2015.02.024
[Indexed for MEDLINE]
Free PMC Article

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