Optogenetic activation of serotonergic neurons enhances anxiety-like behaviour in mice.
Whether increased serotonin (5-HT) release in the forebrain attenuates or enhances anxiety has been controversial for over 25 yr. Although there is considerable indirect evidence, there is no direct evidence that indicates a relationship between acute 5-HT release and anxiety. In particular, there is no known method that can reversibly, selectively, and temporally control serotonergic activity. To address this issue, we generated transgenic animals to manipulate the firing rates of central 5-HT neurons by optogenetic methods. Activation of serotonergic neurons in the median raphe nucleus was correlated to enhanced anxiety-like behaviour in mice, whereas activation of serotonergic neurons in the dorsal raphe nucleus had no effect on anxiety-like behaviour. These results indicate that an acute increase in 5-HT release from the median raphe nucleus enhances anxiety.
Department of Neuropharmacology,Hokkaido University Graduate School of Medicine,N15 W7 Kita-ku, Sapporo, 060-8638,Japan.
Yu
Y
Ohmura
Department of Neuropsychiatry, School of Medicine,Keio University,Tokyo,Japan.
Kenji F
KF
Tanaka
Department of Neuroscience II, Research Institute of Environmental Medicine (RIEM),Nagoya University,Nagoya, 464-8601,Japan.
Tomomi
T
Tsunematsu
Department of Neuroscience II, Research Institute of Environmental Medicine (RIEM),Nagoya University,Nagoya, 464-8601,Japan.
Akihiro
A
Yamanaka
Department of Neuropharmacology,Hokkaido University Graduate School of Medicine,N15 W7 Kita-ku, Sapporo, 060-8638,Japan.
Mitsuhiro
M
Yoshioka
D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017551:Microdialysis; D066267:Midbrain Raphe Nuclei / Q000166:cytology*; D009154:Mutation / Q000235:genetics; D062308:Optogenetics; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase