Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding

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Zona incerta neurons projecting to the ventral tegmental area promote action initiation towards feeding

de Git, K. C. G. (författare)

Hazelhoff, E. M. (författare)

Nota, M. H. C. (författare)

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Schele, Erik (författare): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology

Luijendijk, M. C. M. (författare)

Dickson, Suzanne L., 1966 (författare): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology

van der Plasse, G. (författare)

Adan, R. A. H. (författare)

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(creator_code:org_t)

2020-12-22
2021
Engelska.
Ingår i: Journal of Physiology-London. - : Wiley. - 0022-3751 .- 1469-7793. ; 559:2, s. 709-724

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Abstract Ämnesord

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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. 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

DREADD
feeding
motivation
tetanus toxin light chain
ventral
tegmental area
zona incerta
dopamine neurons
mesolimbic dopamine
parkinsons-disease
weight-gain
food
activation
obesity
reward
motivation
addiction
Neurosciences & Neurology
Physiology

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Av författaren/redakt...: de Git, K. C. G.; Hazelhoff, E. M.; Nota, M. H. C.; Schele, Erik; Luijendijk, M. C ...; Dickson, Suzanne ...; visa fler...; van der Plasse, ...; Adan, R. A. H.; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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Av lärosätet: Göteborgs universitet

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