title: Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards.
abstract: Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals' patience to wait for a delayed reward.
authors.affiliation: Neural Computation Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.
authors.forename: Kayoko W
authors.initials: KW
authors.lastname: Miyazaki
authors.affiliation: Neural Computation Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan. Electronic address: miyazaki@oist.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.affiliation: Mouse Genomics Resource Laboratory, National Institute of Genetics, Mishima 411-8540, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Tabuchi
authors.affiliation: Neural Computation Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Doya
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D000075402:Channelrhodopsins; D003463:Cues; D065847:Dorsal Raphe Nucleus / Q000166:cytology / Q000528:radiation effects*; D008027:Light; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis; D062308:Optogenetics; D012054:Reinforcement, Psychology; D012201:Reward; D059326:Serotonergic Neurons / Q000502:physiology / Q000528:radiation effects*; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000075402:Channelrhodopsins; D012701:Serotonin