Decoding Neural Circuits that Control Compulsive Sucrose Seeking
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 seeki...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/102522 https://orcid.org/0000-0002-0438-3163 https://orcid.org/0000-0003-2527-3382 https://orcid.org/0000-0001-6754-0333 https://orcid.org/0000-0003-2154-6224 https://orcid.org/0000-0002-3854-5968 https://orcid.org/0000-0002-4506-8813 |
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| author | Matthews, Gillian A. Presbrey, Kara N. Wichmann, Romy Wildes, Craig P. Nieh, Horng-An Edward Allsop, Stephen Azariah Leppla, Christopher Albert Neve, Rachael L. Tye, Kay Matthews, Gillian A. Presbrey, Kara N. Wildes, Craig P. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Matthews, Gillian A. Presbrey, Kara N. Wichmann, Romy Wildes, Craig P. Nieh, Horng-An Edward Allsop, Stephen Azariah Leppla, Christopher Albert Neve, Rachael L. Tye, Kay Matthews, Gillian A. Presbrey, Kara N. Wildes, Craig P. |
| author_sort | Matthews, Gillian A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:02:05Z |
| format | Article |
| id | mit-1721.1/102522 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:02:05Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1025222022-09-30T12:58:55Z Decoding Neural Circuits that Control Compulsive Sucrose Seeking Matthews, Gillian A. Presbrey, Kara N. Wichmann, Romy Wildes, Craig P. Nieh, Horng-An Edward Allsop, Stephen Azariah Leppla, Christopher Albert Neve, Rachael L. Tye, Kay Matthews, Gillian A. Presbrey, Kara N. Wildes, Craig P. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Nieh, Horng-An Edward Matthews, Gillian A. Allsop, Stephen Azariah Presbrey, Kara N. Leppla, Christopher Albert Wichmann, Romy Neve, Rachael L. Wildes, Craig P. Tye, Kay 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. JPB Foundation Whitehall Foundation Klingenstein Foundation Brain & Behavior Research Foundation (Young Investigator Award) Alfred P. Sloan Foundation National Institute of Mental Health (U.S.) (NIH R01-MH102441-01) National Institutes of Health (U.S.) (Director’s New Investigator Award DP2-DK-102256-01) National Science Foundation (U.S.). Graduate Research Fellowship Integrative Neuronal Systems Fellowship Training Program in the Neurobiology of Learning and Memory Massachusetts Institute of Technology. Simons Center for the Social Brain (Postdoctoral Fellowship) Jeffrey and Nancy Halis Fellowship Henry E. Singleton Fund James R. Killian Fellowship NWO of the Netherlands (Rubicon Award) 2016-05-18T14:23:02Z 2016-05-18T14:23:02Z 2015-01 2014-11 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/102522 Nieh, Edward H., Gillian A. Matthews, Stephen A. Allsop, Kara N. Presbrey, Christopher A. Leppla, Romy Wichmann, Rachael Neve, Craig P. Wildes, and Kay M. Tye. “Decoding Neural Circuits That Control Compulsive Sucrose Seeking.” Cell 160, no. 3 (January 2015): 528–541. https://orcid.org/0000-0002-0438-3163 https://orcid.org/0000-0003-2527-3382 https://orcid.org/0000-0001-6754-0333 https://orcid.org/0000-0003-2154-6224 https://orcid.org/0000-0002-3854-5968 https://orcid.org/0000-0002-4506-8813 en_US http://dx.doi.org/10.1016/j.cell.2015.01.003 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Matthews, Gillian A. Presbrey, Kara N. Wichmann, Romy Wildes, Craig P. Nieh, Horng-An Edward Allsop, Stephen Azariah Leppla, Christopher Albert Neve, Rachael L. Tye, Kay Matthews, Gillian A. Presbrey, Kara N. Wildes, Craig P. Decoding Neural Circuits that Control Compulsive Sucrose Seeking |
| title | Decoding Neural Circuits that Control Compulsive Sucrose Seeking |
| title_full | Decoding Neural Circuits that Control Compulsive Sucrose Seeking |
| title_fullStr | Decoding Neural Circuits that Control Compulsive Sucrose Seeking |
| title_full_unstemmed | Decoding Neural Circuits that Control Compulsive Sucrose Seeking |
| title_short | Decoding Neural Circuits that Control Compulsive Sucrose Seeking |
| title_sort | decoding neural circuits that control compulsive sucrose seeking |
| url | http://hdl.handle.net/1721.1/102522 https://orcid.org/0000-0002-0438-3163 https://orcid.org/0000-0003-2527-3382 https://orcid.org/0000-0001-6754-0333 https://orcid.org/0000-0003-2154-6224 https://orcid.org/0000-0002-3854-5968 https://orcid.org/0000-0002-4506-8813 |
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