Testing serotonin hypothesis of depression with optogenetics

• Project/Area Number: 25713043
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Hokkaido University
• Principal Investigator: Ohmura Yu 北海道大学, 医学(系)研究科(研究院), 助教 (80597659)
• Research Collaborator: TANAKA KENJI 慶應義塾大学, 医学部, 准教授 (30329700) ; YAMANAKA AKIHIRO 名古屋大学, 環境医学研究所, 教授 (60323292)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
• Keywords: うつ病 / 光遺伝学 / 精神薬理学 / 神経科学

Outline of Final Research Achievements

“Serotonin hypothesis of depression” - decreased serotonin levels in the brain cause depression while increased serotonin levels in the brain attenuate depression - has been widely believed. However there is so far no direct evidence proving the relationships between serotonin and depression/depressive symptoms though the hypothesis was proposed in the 1950s. We addressed this issue by using recently-developed optogenetic tools. We used transgenic mice to manipulate serotonergic activity with light illumination. Our results demonstrated that optogenetic activation of serotonergic neurons decreased depressive-like behavior in mice while optogenetic suppression of serotonergic neurons did not affect it.

Research Products

• [Journal Article] Varenicline Provokes Impulsive Action by Stimulating α4β2 Nicotinic Acetylcholine Receptors in the Infralimbic Cortex in a Nicotine Exposure Status-Dependent Manner. (2017)
  • Author(s): Ohmura Y, Sasamori H, Tsutsui-Kimura I,Izumi T, Yoshida T, Yoshioka M.
  • Journal Title: Pharmacology, Biochemistry and Behavior Volume: 154 Pages: 1-10
  • DOI: 10.1016/j.pbb.2017.01.002
  • NAID: 120006401453
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Raphe serotonergic system modulating emotion — anxiety and fear memory (2017)
  • Author(s): 大村優、吉岡充弘
  • Journal Title: Folia Pharmacologica Japonica Volume: 149 Issue: 1 Pages: 27-33
  • DOI: 10.1254/fpj.149.27
  • NAID: 130005188232
  • ISSN: 0015-5691, 1347-8397
• [Journal Article] The role of serotonergic mechanism in the rat prefrontal cortex for controlling the micturition reflex: An in vivo microdialysis study. (2016)
  • Author(s): Chiba H, Mitsui T, Kitta T, Ohmura Y, Moriya K, Kanno Y, Yoshioka M, Shinohara N
  • Journal Title: Neurourology and Urodynamics Volume: 35 Issue: 8 Pages: 902-907
  • DOI: 10.1002/nau.22843
  • Peer Reviewed
• [Journal Article] Neuronal codes for the inhibitory control of impulsive actions in the rat infralimbic cortex (2016)
  • Author(s): Tsutsui-Kimura I., Ohmura Y., Izumi T., Matsushima T., Amita H., Yamaguchi T., Yoshida T, Yoshioka M.
  • Journal Title: Behavioural Brain Research Volume: 296 Pages: 361-372
  • DOI: 10.1016/j.bbr.2015.08.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food seeking behavior while reducing impulsivity in the absence of an effect on food intake (2016)
  • Author(s): Warthen D, Lambeth P, Ottolini M, Shi Y, Barker B, Gaykema R, Newmyer B, Ohmura Y, Perez-Reyes E, Guler A, Patel M, Scott M.
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 10
  • DOI: 10.3389/fnbeh.2016.00063
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Serotonin 5-HT7 receptor in the ventral hippocampus modulates the retrieval of fear memory and stress-induced defecation. (2015)
  • Author(s): Ohmura Y, Yoshida T, Konno K, Minami M, Watanabe M, Yoshioka M.
  • Journal Title: Int J Neuropsychopharmacol. Volume: pyv131 Pages: 1-12
  • DOI: 10.1093/ijnp/pyv131
  • NAID: 120005866845
  • Peer Reviewed / Open Access
• [Journal Article] Repeated fluvoxamine treatment recovers juvenile stress-induced morphological changes and depressive-like behavior in rats (2015)
  • Author(s): Lyttle K, Ohmura Y, Konno K, Yoshida T, Izumi T, Watanabe M, Yoshioka M.
  • Journal Title: Brain Research Volume: 1616 Pages: 88-100
  • DOI: 10.1016/j.brainres.2015.04.058
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Optogenetic activation of serotonergic neurons enhances anxiety-like behavior in mice. (2014)
  • Author(s): Ohmura Y, Tanaka KF, Tsunematsu T, Yamanaka A,Yoshioka M
  • Journal Title: Int J Neuropsychopharmacology Volume: 17 Issue: 11 Pages: 1777-1783
  • DOI: 10.1017/s1461145714000637
  • Peer Reviewed / Open Access
• [Journal Article] Milnacipran remediates impulsive deficits in rats with lesions of the ventromedial prefrontal cortex (2014)
  • Author(s): Tsutsui-Kimura I, Yoshida T, Ohmura Y, Izumi T, Yoshioka M
  • Journal Title: The international journal of neuropsychopharmacology Volume: 8 Issue: 5 Pages: 1-14
  • DOI: 10.1093/ijnp/pyu083
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Optogenetic Activation of Serotonergic Neurons Enhances Anxiety-Like Behavior in Mice. (2014)
  • Author(s): Ohmura Y, Tanaka F K, Tsunematsu T, Yamanaka A, Yoshioka M
  • Journal Title: International Journal of Neuropsychopharmacology Volume: 未定
  • Peer Reviewed
• [Presentation] 恐怖記憶の想起・消去に関わるセロトニン神経系回路 (2017)
  • Author(s): 大村優，吉田隆行，吉岡充弘
  • Organizer: 第90回日本薬理学会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
• [Presentation] 縫線核セロトニン神経による情動調節機構－光遺伝学を用いてー (2016)
  • Author(s): 大村 優
  • Organizer: 第89回日本薬理学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-03-11
• [Presentation] 光遺伝学による中枢セロトニン神経の操作は不安および衝動性を変化させる (2014)
  • Author(s): 大村 優, 田中 謙二, 木村 生, 常松 友美, 山中 章弘, 吉岡 充弘
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-11
• [Presentation] 光遺伝学による中枢セロトニン神経の選択的制御を用いてセロトニン再取り込み阻害薬の作用機序を考える (2014)
  • Author(s): 大村 優
  • Organizer: 第87回日本薬理学会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] 衝動性抑制薬とその作用機序 (2013)
  • Author(s): 大村 優
  • Organizer: 第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会 合同年会
  • Place of Presentation: 沖縄コンベンションセンター（宜野湾市）
• [Remarks] Yu Ohmura's web page
  • URL: http://www.geocities.jp/neuropharmacology_yuohmura/