TY - JOUR
T1 - An orexigenic subnetwork within the human hippocampus
AU - Barbosa, Daniel A.N.
AU - Gattas, Sandra
AU - Salgado, Juliana S.
AU - Kuijper, Fiene Marie
AU - Wang, Allan R.
AU - Huang, Yuhao
AU - Kakusa, Bina
AU - Leuze, Christoph
AU - Luczak, Artur
AU - Rapp, Paul
AU - Malenka, Robert C.
AU - Hermes, Dora
AU - Miller, Kai J.
AU - Heifets, Boris D.
AU - Bohon, Cara
AU - McNab, Jennifer A.
AU - Halpern, Casey H.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/9/14
Y1 - 2023/9/14
N2 - Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing 1–4. 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 hormone 5,6. 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.
AB - Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing 1–4. 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 hormone 5,6. 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.
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U2 - 10.1038/s41586-023-06459-w
DO - 10.1038/s41586-023-06459-w
M3 - Article
C2 - 37648849
AN - SCOPUS:85169317881
SN - 0028-0836
VL - 621
SP - 381
EP - 388
JO - Nature
JF - Nature
IS - 7978
ER -