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Stimulation of VTA dopamine inputs to LH upregulates orexin neuronal activity in a DRD2-dependent manner


Harada, Masaya; Capdevila, Laia Serratosa; Wilhelm, Maria; Burdakov, Denis; Patriarchi, Tommaso (2023). Stimulation of VTA dopamine inputs to LH upregulates orexin neuronal activity in a DRD2-dependent manner. eLife, (20):Epub ahead of print.

Abstract

Dopamine and orexins (hypocretins) play important roles in regulating reward-seeking behaviors. It is known that hypothalamic orexinergic neurons project to dopamine neurons in the ventral tegmental area (VTA), where they can stimulate dopaminergic neuronal activity. Although there are reciprocal connections between dopaminergic and orexinergic systems, whether and how dopamine regulates the activity of orexin neurons is currently not known. Here we implemented an opto-Pavlovian task in which mice learn to associate a sensory cue with optogenetic dopamine neuron stimulation to investigate the relationship between dopamine release and orexin neuron activity in the LH. We found that dopamine release can be evoked in LH upon optogenetic stimulation of VTA dopamine neurons, and is also naturally evoked by cue presentation after opto-Pavlovian learning. Furthermore, orexin neuron activity could also be upregulated by local stimulation of dopaminergic terminals in the LH in a way that is partially dependent on dopamine D2 receptors (DRD2). Our results reveal previously unknown orexinergic coding of reward expectation and unveil an orexin-regulatory axis mediated by local dopamine inputs in the LH.
Optical VTA DA neuron stimulation is sufficient to elicit a Pavlovian-like dopamine transient in the NAc
Dopamine in the LH encodes both negative and positive reward prediction errors
Dopamine in the LH positively modulates orexin neuronal activity locally in a D2R dependent way

Abstract

Dopamine and orexins (hypocretins) play important roles in regulating reward-seeking behaviors. It is known that hypothalamic orexinergic neurons project to dopamine neurons in the ventral tegmental area (VTA), where they can stimulate dopaminergic neuronal activity. Although there are reciprocal connections between dopaminergic and orexinergic systems, whether and how dopamine regulates the activity of orexin neurons is currently not known. Here we implemented an opto-Pavlovian task in which mice learn to associate a sensory cue with optogenetic dopamine neuron stimulation to investigate the relationship between dopamine release and orexin neuron activity in the LH. We found that dopamine release can be evoked in LH upon optogenetic stimulation of VTA dopamine neurons, and is also naturally evoked by cue presentation after opto-Pavlovian learning. Furthermore, orexin neuron activity could also be upregulated by local stimulation of dopaminergic terminals in the LH in a way that is partially dependent on dopamine D2 receptors (DRD2). Our results reveal previously unknown orexinergic coding of reward expectation and unveil an orexin-regulatory axis mediated by local dopamine inputs in the LH.
Optical VTA DA neuron stimulation is sufficient to elicit a Pavlovian-like dopamine transient in the NAc
Dopamine in the LH encodes both negative and positive reward prediction errors
Dopamine in the LH positively modulates orexin neuronal activity locally in a D2R dependent way

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:20 July 2023
Deposited On:08 Jan 2024 13:31
Last Modified:08 Jan 2024 13:41
Publisher:eLife Sciences Publications Ltd.
Number of Pages:36
ISSN:2050-084X
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.7554/elife.90158.1
  • Content: Accepted Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
  • Content: Accepted Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)