The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

• Published in: International journal of molecular sciences Vol. 21; no. 6; p. 2160
• Main Authors: Nagai, Yuma, Takayama, Kaito, Nishitani, Naoya, Andoh, Chihiro, Koda, Masashi, Shirakawa, Hisashi, Nakagawa, Takayuki, Nagayasu, Kazuki, Yamanaka, Akihiro, Kaneko, Shuji
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.03.2020; MDPI
• Subjects: Actuators; Animals; Aversion; Basal Forebrain - metabolism; Basal Forebrain - physiology; Behavior; Behavior Rating Scale; Central Amygdaloid Nucleus - metabolism; Central Amygdaloid Nucleus - physiology; Dependovirus - genetics; Dopamine; Dorsal raphe nucleus; Dorsal Raphe Nucleus - metabolism; Dorsal Raphe Nucleus - physiology; Enhancer Elements, Genetic; Genetic Vectors; Hypothalamic Area, Lateral - metabolism; Hypothalamic Area, Lateral - physiology; Light; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurons - metabolism; Neurons - physiology; Nose; Nucleus Accumbens - metabolism; Nucleus Accumbens - physiology; Optogenetics; Place preference conditioning; Promoter Regions, Genetic; Raphe nuclei; Reinforcement; Reward; Rodents; Self-stimulation; Serotonin; Serotonin - metabolism; Serotonin - physiology; Transgenic animals; Transgenic mice; Tryptophan; Tryptophan hydroxylase; Tryptophan Hydroxylase - genetics; Tryptophan Hydroxylase - metabolism; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - physiology; Ventral tegmentum; reward; serotonin; optogenetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21062160

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. 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. 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. 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.