An orexigenic subnetwork within the human hippocampus

Daniel A. N. Barbosa, Sandra Gattas, Juliana S. Salgado, Fiene Marie Kuijper, Allan R. Wang, Yuhao Huang, Bina Kakusa, Christoph Leuze, Artur Luczak, Paul Rapp, Robert C. Malenka, Dora Hermes, Kai J. Miller, Boris D. Heifets, Cara Bohon, Jennifer A. McNab and Casey H. Halpern ()
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Daniel A. N. Barbosa: University of Pennsylvania
Sandra Gattas: University of California, Irvine
Juliana S. Salgado: Stanford University School of Medicine
Fiene Marie Kuijper: Stanford University School of Medicine
Allan R. Wang: Stanford University School of Medicine
Yuhao Huang: Stanford University School of Medicine
Bina Kakusa: Stanford University School of Medicine
Christoph Leuze: Stanford University School of Medicine
Artur Luczak: University of Lethbridge
Paul Rapp: Uniformed Services University
Robert C. Malenka: Stanford University School of Medicine
Dora Hermes: Mayo Clinic
Kai J. Miller: Mayo Clinic
Boris D. Heifets: Stanford University School of Medicine
Cara Bohon: Stanford University School of Medicine
Jennifer A. McNab: Stanford University School of Medicine
Casey H. Halpern: University of Pennsylvania

Nature, 2023, vol. 621, issue 7978, 381-388

Abstract: Abstract Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1–4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

Date: 2023
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DOI: 10.1038/s41586-023-06459-w

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