title: Accumbal D1R Neurons Projecting to Lateral Hypothalamus Authorize Feeding.
abstract: Feeding satisfies metabolic need but is also controlled by external stimuli, like palatability or predator threat. Nucleus accumbens shell (NAcSh) projections to the lateral hypothalamus (LH) are implicated in mediating such feeding control, but the neurons involved and their mechanism of action remain elusive. We show that dopamine D1R-expressing NAcSh neurons (D1R-MSNs) provide the dominant source of accumbal inhibition to LH and provide rapid control over feeding via LH GABA neurons. In freely feeding mice, D1R-MSN activity reduced during consumption, while their optogenetic inhibition prolonged feeding, even in the face of distracting stimuli. Conversely, activation of D1R-MSN terminals in LH was sufficient to abruptly stop ongoing consumption, even during hunger. Direct inhibition of LH GABA neurons, which received input from D1R-MSNs, fully recapitulated these findings. Together, our study resolves a feeding circuit that overrides immediate metabolic need to allow rapid consumption control in response to changing external stimuli. VIDEO ABSTRACT.
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Eoin C
authors.initials: EC
authors.lastname: O'Connor
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Kremer
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lefort
authors.affiliation: CREST Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kawaharacho 53, Shogoin, Sakyo-ku, Kyoto 606-8509, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pascoli
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Clément
authors.initials: C
authors.lastname: Rohner
authors.affiliation: Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland; Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, 1211 Geneva, Switzerland. Electronic address: christian.luscher@unige.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Lüscher
mesh_terms: D000818:Animals; D005247:Feeding Behavior / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D009924:Organ Culture Techniques; D017447:Receptors, Dopamine D1 / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1