The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion
Autor: | Yuma Nagai, Akihiro Yamanaka, Masashi Koda, Takayuki Nakagawa, Hisashi Shirakawa, Kaito Takayama, Shuji Kaneko, Chihiro Andoh, Kazuki Nagayasu, Naoya Nishitani |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Stimulation Tryptophan Hydroxylase Nucleus Accumbens lcsh:Chemistry Mice 0302 clinical medicine Promoter Regions Genetic lcsh:QH301-705.5 Spectroscopy reward Neurons TPH2 General Medicine Dependovirus Computer Science Applications serotonin Ventral tegmental area medicine.anatomical_structure Enhancer Elements Genetic psychological phenomena and processes Dorsal Raphe Nucleus Basal Forebrain Genetic Vectors Mice Transgenic Biology Optogenetics Catalysis Article Inorganic Chemistry 03 medical and health sciences Dorsal raphe nucleus medicine Animals Physical and Theoretical Chemistry optogenetics Molecular Biology Organic Chemistry Central Amygdaloid Nucleus Ventral Tegmental Area Tryptophan hydroxylase Conditioned place preference Mice Inbred C57BL 030104 developmental biology nervous system lcsh:Biology (General) lcsh:QD1-999 Hypothalamic Area Lateral Behavior Rating Scale Serotonin Neuroscience 030217 neurology & neurosurgery |
Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6, p 2160 (2020) International Journal of Molecular Sciences Volume 21 Issue 6 |
ISSN: | 1422-0067 |
Popis: | Background: Reward processing is fundamental for animals to survive and reproduce. Many studies have shown the importance of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons in this process, but the strongly correlative link between the activity of DRN 5-HT neurons and rewarding/aversive potency is under debate. Our primary objective was to reveal this link using two different strategies to transduce DRN 5-HT neurons. Methods: For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. For transduction in Tph2-tTA transgenic mice, AAVs bearing the tTA-dependent TetO enhancer were used. To manipulate the activity of 5-HT neurons, optogenetic actuators (CheRiff, eArchT) were expressed by AAVs. For measurement of rewarding/aversive potency, we performed a nose-poke self-stimulation test and conditioned place preference (CPP) test. Results: We found that stimulation of DRN 5-HT neurons and their projections to the ventral tegmental area (VTA) increased the number of nose-pokes in self-stimulation test and CPP scores in both targeting methods. Concomitantly, CPP scores were decreased by inhibition of DRN 5-HT neurons and their projections to VTA. Conclusion: Our findings indicate that the activity of DRN 5-HT neurons projecting to the VTA is a key modulator of balance between reward and aversion. |
Databáze: | OpenAIRE |
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