Decoding Neural Circuits that Control Compulsive Sucrose Seeking
Open accessAbstract
The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to reward processing, but the computations within the LH-VTA loop that give rise to specific aspects of behavior have been difficult to isolate. We show that LH-VTA neurons encode the learned action of seeking a reward, independent of reward availability. In contrast, LH neurons downstream of VTA encode reward-predictive cues and unexpected reward omission. We show that inhibiting the LH-VTA pathway reduces "compulsive" sucrose seeking but not food consumption in hungry mice. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feeding-related behavior. Our study overlays information about the type, function, and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.
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Disinhibition of VTA dopamine neurons enhances motivation towards a variety of stimuli ranging from social stimuli to novel objects.
“The disinhibition of VTA dopamine neurons, for example, has been shown to enhance motivation towards a variety of stimuli ranging from social stimuli to novel objects182,183.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [182]
Distinct neural circuits motivate food consumption related to the rewarding value of food.
“distinct neural circuits are thought to motivate food consumption related to the rewarding value of food (Nieh et al., 2015)”
From Dorsal raphe dopamine neurons represent the experience of social isolation (2016) · cites this paper as Nieh et al., 2015
Stimulation of lateral hypothalamic terminals in the ventral tegmental area promotes sucrose seeking even when mice must cross an electrified floor to obtain the sucrose reward.
“Stimulation of lateral hypothalamic terminals in the VTA, for example, promotes sucrose seeking, even when mice must cross an electrified floor to obtain the sucrose reward128.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [128]
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- Authors
- Nieh, E. H., Matthews, G. A., Allsop, S. A., Presbrey, K. N., Leppla, C. A., Wichmann, R., Neve, R., Wildes, C. P., & Tye, K. M.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Tye, Kay M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 160
- Issue
- 3
- Pages
- 528-541
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4312417
- OpenAlex
- W2147755305
- Cited by
- 402
- References
- 48
- Citations by year
- 2026: 20 · 2025: 36 · 2024: 33 · 2023: 33 · 2022: 28 · 2021: 39 · 2020: 30 · 2019: 35 · 2018: 38 · 2017: 41 · 2016: 35 · 2015: 32 · 2012: 1
- FWCI
- 22.60
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-06-04)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (R01MH102441, T32MH074249, R01‐MH102441‐01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2-DK-102256-01, DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- lateral hypothalamus, ventral tegmental area, reward processing, dopaminergic neurons, GABAergic neurons, reward omission, reward-predictive cues, compulsive eating, feeding behavior, neural circuits, mice
- MeSH terms
- Animals, Behavior, Animal, Feedback, gamma-Aminobutyric Acid, Hypothalamic Area, Lateral, Models, Neurological, Neural Pathways, Neurons, Reward, Sucrose, Ventral Tegmental Area, Mice
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