Sensory-experience dependent development of olfactory bulb interneurons

• Project/Area Number: 25430010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Nara Medical University
• Principal Investigator: YOSHIHARA SEIICHI 奈良県立医科大学, 医学部, 講師 (90360669)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI HIROO 奈良県立医科大学, 医学部, 助教 (20390685)
• Co-Investigator(Renkei-kenkyūsha): TSUBOI AKIO 奈良県立医科大学, 医学部, 教授 (20163868)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 成体神経新生 / 嗅球介在ニューロン / シナプス形成 / 転写因子 / 嗅球 / Npas4 / 神経活動依存的な発達 / スパイン / 介在ニューロン

Outline of Final Research Achievements

Sensory experience regulates development in olfactory bulb (OB). Recently, we identified a transcription factor, neuronal Per/Arnt/Sim domain protein 4 (Npas4) gene, which is expressed in a subset of OB GCs following sensory experience. Npas4 overexpression in newborn OB GCs increased the spine density even under sensory deprivation. Conversely, both Npas4 knockdown and knockout resulted in a significant reduction in the spine density of OB GCs. Then, to investigate molecules that play a role in the downstream of Npas4, we searched for microRNAs (miRs), whose expression levels differed between the wild-type and Npas4-knockout OBs, and whose expression correlated with the interneurons, based on RNA-sequencing plus in situ hybridization screenings. Among ~50 miRs, we found that three novel miRs show a clear difference in expression between the wild-type and Npas4-knockout OBs.

Research Products

• [Journal Article] Molecular mechanisms regulating the dendritic development of newborn olfactory bulb interneurons in a sensory experience-dependent manner. (2016)
  • Author(s): Yoshihara S, Takahashi H and Tsuboi A.
  • Journal Title: Frontiers in Neuroscience Volume: 9 Pages: 514-514
  • DOI: 10.3389/fnins.2015.00514
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Npas4 regulates Mdm2 and thus Dcx in experience-dependent olfactory bulb interneuron dendritic spine development. (2014)
  • Author(s): Yoshihara S, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Kitsuki M, Tatsumi K, Furukawa-Hibi Y, Hirai H, Nagai T, Yamada K and Tsuboi A.
  • Journal Title: Cell Reports Volume: 8 Issue: 3 Pages: 843-857
  • DOI: 10.1016/j.celrep.2014.06.056
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 嗅球ニューロンにおける匂い刺激依存的なシナプス形成の分子機構 (2014)
  • Author(s): 吉原誠一，高橋弘雄，坪井昭夫.
  • Journal Title: AROMA RESEARCH Volume: 15 Pages: 248-249
  • Peer Reviewed
• [Journal Article] Goofy coordinates the acuity of olfactory signaling (2013)
  • Author(s): Kaneko-Goto T, Sato Y, Katada S, Kinameri E, Yoshihara S, Nishiyori A, Kimura M, Fujita H, Touhara K, Reed RR, Yoshihara Y
  • Journal Title: Journal of Neuroscience Volume: 33 Issue: 32 Pages: 12987-12996
  • DOI: 10.1523/jneurosci.4948-12.2013
  • Peer Reviewed
• [Presentation] A specific subtype of newborn interneurons in the olfactory bulb is required for behaviors on odor detection and discrimination. (2016)
  • Author(s): Takahashi H, Yoshihara S, Ogawa Y, Asahina R, Kinoshita M and Tsuboi A.
  • Organizer: Fusion Conference on Neurogenesis: Implications for Lifelong Development and Disease
  • Place of Presentation: Cancun, Mexico
  • Year and Date: 2016-03-02
  • Int'l Joint Research
• [Presentation] MicroRNAs downstream of Npas4 that regulates the sensory experience-dependent development of dendritic spines in newborn olfactory bulb interneurons. (2015)
  • Author(s): Yoshihara S, Takahashi H, Kinoshita M, Asahina R and Tsuboi A.
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2015-12-01
• [Presentation] MicroRNAs downstream of Npas4 that regulates the sensory experience-dependent development of dendritic spines in newborn olfactory bulb interneurons. (2015)
  • Author(s): Yoshihara S, Takahashi H, Kinoshita M, Asahina R and Tsuboi A.
  • Organizer: 第38回日本神経科学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2015-07-28
• [Presentation] Transcription factor Npas4 regulates the sensory experience-dependent development of dendritic spines in newborn olfactory bulb interneurons (2015)
  • Author(s): Yoshihara S, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Furukawa-Hibi Y, Nagai T, Yamada K and Tsuboi A.
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Transcription factor Npas4 regulates the sensory experience-dependent development of dendritic spines in newborn olfactory bulb interneurons. (2014)
  • Author(s): Yoshihara S, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Furukawa-Hibi Y, Nagai T, Yamada K and Tsuboi A.
  • Organizer: 第37回日本分子生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Transcription factor Npas4 regulates the sensory experience-dependent development of dendritic spines in newborn olfactory bulb interneurons. (2014)
  • Author(s): Yoshihara S, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Furukawa-Hibi Y, Nagai T, Yamada K and Tsuboi A.
  • Organizer: 第37回日本神経科学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Npas4 regulates the sensory experience-dependent development of dendritic spines in newborn olfactory bulb interneurons. (2014)
  • Author(s): Yoshihara S, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Furukawa-Hibi Y, Nagai T, Yamada K and Tsuboi A.
  • Organizer: Cold Spring Harbor Meeting: Neuronal Circuits
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2014-04-02 – 2014-04-05
• [Presentation] Sensory input regulates the dendritic development of specific neuronal subtypes in the mouse olfactory bulb. (2013)
  • Author(s): Yoshihara S, Takahashi H, Kinoshita M, Nishimura N and Tsuboi A.
  • Organizer: Cold Spring Harbor Asia Conference, Francis Crick Symposium on Neuroscience: The Changing Brain
  • Place of Presentation: Suzhou Dushu Lake Conference Center, China
• [Presentation] Npas4 regulates sensory experience-dependent development of dendritic spines in olfactory bulb granule cells. (2013)
  • Author(s): Yoshihara S, Takahashi H, Kinoshita M, Nishimura N and Tsuboi A.
  • Organizer: 神経の再生と分化に関する国際シンポジウム Neurogenesis 2013
  • Place of Presentation: 松島、宮城県
• [Book] Electroporation Methods in Neuroscience (Neuromethods) (2015)
  • Author(s): Takahashi H, Yoshihara S, Asahina R, Tamada Y and Tsuboi A.
  • Total Pages: 199
  • Publisher: Humana Press
• [Remarks] 奈良県立医科大学 先端医科学研究機構 脳神経システム医科学
  • URL: http://www.naramed-u.ac.jp/~amrc-lab1/publication2.html
• [Remarks] 奈良県立医科大学 先端医学研究機構 脳神経システム医科学
  • URL: http://www.naramed-u.ac.jp/~amrc-lab1/tsuboi%20Lab3.html