Hypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone

Emily E. Noble, Zhuo Wang, Clarissa M. Liu, Elizabeth A. Davis, Andrea N. Suarez, Lauren M. Stein, Linda Tsan, Sarah J. Terrill, Ted M. Hsu, A-Hyun Jung, Lauren M. Raycraft, Joel D. Hahn, Martin Darvas, Alyssa M. Cortella, Lindsey A. Schier, Alexander W. Johnson, Matthew R. Hayes, Daniel P. Holschneider and Scott E. Kanoski ()
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Emily E. Noble: University of Southern California
Zhuo Wang: University of Southern California
Clarissa M. Liu: University of Southern California
Elizabeth A. Davis: University of Southern California
Andrea N. Suarez: University of Southern California
Lauren M. Stein: University of Pennsylvania
Linda Tsan: University of Southern California
Sarah J. Terrill: University of Southern California
Ted M. Hsu: University of Illinois at Chicago
A-Hyun Jung: University of Southern California
Lauren M. Raycraft: Michigan State University
Joel D. Hahn: University of Southern California
Martin Darvas: University of Washington
Alyssa M. Cortella: University of Southern California
Lindsey A. Schier: University of Southern California
Alexander W. Johnson: Michigan State University
Matthew R. Hayes: University of Pennsylvania
Daniel P. Holschneider: University of Southern California
Scott E. Kanoski: University of Southern California

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Behavioral impulsivity is common in various psychiatric and metabolic disorders. Here we identify a hypothalamus to telencephalon neural pathway for regulating impulsivity involving communication from melanin-concentrating hormone (MCH)-expressing lateral hypothalamic neurons to the ventral hippocampus subregion (vHP). Results show that both site-specific upregulation (pharmacological or chemogenetic) and chronic downregulation (RNA interference) of MCH communication to the vHP increases impulsive responding in rats, indicating that perturbing this system in either direction elevates impulsivity. Furthermore, these effects are not secondary to either impaired timing accuracy, altered activity, or increased food motivation, consistent with a specific role for vHP MCH signaling in the regulation of impulse control. Results from additional functional connectivity and neural pathway tracing analyses implicate the nucleus accumbens as a putative downstream target of vHP MCH1 receptor-expressing neurons. Collectively, these data reveal a specific neural circuit that regulates impulsivity and provide evidence of a novel function for MCH on behavior.

Date: 2019
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DOI: 10.1038/s41467-019-12895-y

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