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Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding
KEY POINTS: The zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding. We experimentally (in)activated the ZI to VTA projection...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839680/ https://www.ncbi.nlm.nih.gov/pubmed/33296086 http://dx.doi.org/10.1113/JP276513 |
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author | de Git, Kathy C.G. Hazelhoff, Esther M. Nota, Minke H.C. Schele, Erik Luijendijk, Mieneke C.M. Dickson, Suzanne L. van der Plasse, Geoffrey Adan, Roger A.H. |
author_facet | de Git, Kathy C.G. Hazelhoff, Esther M. Nota, Minke H.C. Schele, Erik Luijendijk, Mieneke C.M. Dickson, Suzanne L. van der Plasse, Geoffrey Adan, Roger A.H. |
author_sort | de Git, Kathy C.G. |
collection | PubMed |
description | KEY POINTS: The zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding. We experimentally (in)activated the ZI to VTA projection by using dual viral vector technology, and studied the effects on feeding microstructure, the willingness to work for food, general activity and body temperature. Activity of the ZI to VTA projection promotes feeding by facilitating action initiation towards food, as reflected in meal frequency and the willingness to work for food reward, without affecting general activity or directly modulating body temperature. We show for the first time that activity of the ZI to VTA projection promotes feeding, which improves the understanding of the neurobiology of feeding behaviour and body weight regulation. ABSTRACT: Both the zona incerta (ZI) and the ventral tegmental area (VTA) have been implicated in feeding behaviour. The ZI provides prominent input to the VTA, although it has not yet been investigated whether this projection regulates feeding. Therefore, we investigated the role of ZI to VTA projection neurons in the regulation of several aspects of feeding behaviour. We determined the effects of (in)activation of ZI to VTA projection neurons on feeding microstructure, food‐motivated behaviour under a progressive ratio schedule of reinforcement, locomotor activity and core body temperature. To activate or inactivate ZI neurons projecting to the VTA, we used a combination of canine adenovirus‐2 in the VTA, as well as Cre‐dependent designer receptors exclusively activated by designer drugs (DREADD) or tetanus toxin (TetTox) light chain in the ZI. TetTox‐mediated inactivation of ZI to VTA projection neurons reduced food‐motivated behaviour and feeding by reducing meal frequency. Conversely, DREADD‐mediated chemogenetic activation of ZI to VTA projection neurons promoted food‐motivated behaviour and feeding. (In)activation of ZI to VTA projection neurons did not affect locomotor activity or directly regulate core body temperature. Taken together, ZI neurons projecting to the VTA exert bidirectional control overfeeding behaviour. More specifically, activity of ZI to VTA projection neurons facilitate action initiation towards feeding, as reflected in both food‐motivated behaviour and meal initiation, without affecting general activity. |
format | Online Article Text |
id | pubmed-7839680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78396802021-02-02 Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding de Git, Kathy C.G. Hazelhoff, Esther M. Nota, Minke H.C. Schele, Erik Luijendijk, Mieneke C.M. Dickson, Suzanne L. van der Plasse, Geoffrey Adan, Roger A.H. J Physiol Neuroscience KEY POINTS: The zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding. We experimentally (in)activated the ZI to VTA projection by using dual viral vector technology, and studied the effects on feeding microstructure, the willingness to work for food, general activity and body temperature. Activity of the ZI to VTA projection promotes feeding by facilitating action initiation towards food, as reflected in meal frequency and the willingness to work for food reward, without affecting general activity or directly modulating body temperature. We show for the first time that activity of the ZI to VTA projection promotes feeding, which improves the understanding of the neurobiology of feeding behaviour and body weight regulation. ABSTRACT: Both the zona incerta (ZI) and the ventral tegmental area (VTA) have been implicated in feeding behaviour. The ZI provides prominent input to the VTA, although it has not yet been investigated whether this projection regulates feeding. Therefore, we investigated the role of ZI to VTA projection neurons in the regulation of several aspects of feeding behaviour. We determined the effects of (in)activation of ZI to VTA projection neurons on feeding microstructure, food‐motivated behaviour under a progressive ratio schedule of reinforcement, locomotor activity and core body temperature. To activate or inactivate ZI neurons projecting to the VTA, we used a combination of canine adenovirus‐2 in the VTA, as well as Cre‐dependent designer receptors exclusively activated by designer drugs (DREADD) or tetanus toxin (TetTox) light chain in the ZI. TetTox‐mediated inactivation of ZI to VTA projection neurons reduced food‐motivated behaviour and feeding by reducing meal frequency. Conversely, DREADD‐mediated chemogenetic activation of ZI to VTA projection neurons promoted food‐motivated behaviour and feeding. (In)activation of ZI to VTA projection neurons did not affect locomotor activity or directly regulate core body temperature. Taken together, ZI neurons projecting to the VTA exert bidirectional control overfeeding behaviour. More specifically, activity of ZI to VTA projection neurons facilitate action initiation towards feeding, as reflected in both food‐motivated behaviour and meal initiation, without affecting general activity. John Wiley and Sons Inc. 2020-12-22 2021-01-15 /pmc/articles/PMC7839680/ /pubmed/33296086 http://dx.doi.org/10.1113/JP276513 Text en © 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Neuroscience de Git, Kathy C.G. Hazelhoff, Esther M. Nota, Minke H.C. Schele, Erik Luijendijk, Mieneke C.M. Dickson, Suzanne L. van der Plasse, Geoffrey Adan, Roger A.H. Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
title | Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
title_full | Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
title_fullStr | Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
title_full_unstemmed | Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
title_short | Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
title_sort | zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839680/ https://www.ncbi.nlm.nih.gov/pubmed/33296086 http://dx.doi.org/10.1113/JP276513 |
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