Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation
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Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic component of the LH-VTA pathway supports positive reinforcement and place preference, while the glutamatergic component mediates place avoidance. In addition, our results indicate that photoactivation of these projections modulates other behaviors, such as social interaction and perseverant investigation of a novel object. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activation across multiple contexts, consistent with a role in increasing motivational salience. VIDEO ABSTRACT.
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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 [183]
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Skinner, M., Daanish, D., Damphousse, C. C., Krohmer, R. W., Mallet, P. E., McKay, B. E., & Miller, N. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.114965 · Cited by 3 · see citing works
- Authors
- Nieh, E. H., Vander Weele, C. M., Matthews, G. A., Presbrey, K. N., Wichmann, R., Leppla, C. A., Izadmehr, E. M., & Tye, K. M.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Tye, Kay M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 90
- Issue
- 6
- Pages
- 1286-1298
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4961212
- OpenAlex
- W2401816914
- Cited by
- 387
- References
- 82
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 40 · 2023: 46 · 2022: 49 · 2021: 50 · 2020: 33 · 2019: 40 · 2018: 29 · 2017: 31 · 2016: 7 · 2012: 1
- FWCI
- 20.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (R01MH102441)
- National Institute of General Medical Sciences (T32GM007484)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- lateral hypothalamus, ventral tegmental area, GABAergic projections, glutamatergic projections, dopamine release, nucleus accumbens, behavioral activation, place preference, place avoidance, positive reinforcement, motivational salience, social interaction, photostimulation
- MeSH terms
- Animals, Avoidance Learning, Behavior, Animal, Dopamine, Hypothalamic Area, Lateral, Neural Inhibition, Nucleus Accumbens, Reward, Ventral Tegmental Area, Mice, Dopaminergic Neurons, GABAergic Neurons
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