| Project/Area Number |
25290015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Nara Medical University |
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Principal Investigator |
Tsuboi Akio 奈良県立医科大学, 医学部, 教授 (20163868)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIHARA SEIICHI 奈良県立医科大学, 医学部, 講師 (90360669)
TAKAHASHI HIROO 奈良県立医科大学, 医学部, 助教 (20390685)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMAI SHOUJI 奈良先端科学技術大学院大学, バイオサイエンス研究科, 准教授 (50420469)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | 成体神経新生 / 嗅球介在ニューロン / 神経活動依存性 / 神経可塑性 / 神経再生 / 嗅覚系 |
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| Outline of Final Research Achievements |
Sensory experience regulates neuronal development in various brain structures, including the cortex, hippocampus and olfactory bulb (OB). However, little is known about the developmental role of sensory experience in major OB populations of inhibitory interneurons, such as granule cells (GCs). In this study, we identified a transcription factor 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, Npas4-KO mice resulted in a significant reduction in the spine density of OB GCs. Furthermore, we identified, as a novel target of Npas4, an E3 ubiquitin ligase Mdm2 gene, which is expressed at low levels in the wild-type OB but at higher levels in the Npas4-KO OB. These results suggest that Npas4 regulates Mdm2 expression to ubiquitinate and degrade a microtubule-associated protein Dcx for shaping the dendritic spines of OB GCs after sensory experience.
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