2012 Fiscal Year Final Research Report
Functional and Phenotypic Regulation of GABAergic Development with Neurotrophic Factors
| Project/Area Number |
22300107
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAMBA Hisaaki 新潟大学, 脳研究所, 助教 (90332650)
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| Co-Investigator(Renkei-kenkyūsha) |
OZAKI Miwako 早稲田大学, 生命医療工学研究所, 教授 (30291058)
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| Project Period (FY) |
2010 – 2012
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| Keywords | GABA / 神経栄養因子 / 脳発達 / 大脳皮質 / 基底核 / 上皮成長因子 / ニューレグリン |
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| Research Abstract |
GABAergic neurons play crucial roles in the brain functions, attenuating excitatoryneurotransmission, generating oscillation activity patterns, and regulating developmentalplasticity and critical periods. Recently, we implicate neurotrophic factors of the EGFfamily in the brain diseases of developmental origin such as autism and schizophrenia. Inthe present project, we planed to explore the physiological activity, cellular signaling, and pathologic contribution of EGF-like factors’ actions on GABAergic neurons and theirsubtype(s). Among various subtypes of cortical GABAergic neurons, parvalbumin-positiveGABA neurons carried ErbB4 and reacted with neuregulin-1. This factor elevated theexpression of AMPA-type glutamate receptors, more efficiently derived GABA release, andproduced stronger postsynaptic inhibition. The same type of GABAergic neurons expressedErbB1 and responded to EGF as well, although the direction of the reaction was totallyopposite; EGF down-regulated the glutamate receptor levels and glutamate aciddecarboxylase expression, provoking more modest inhibition in postsynaptic neurons. Incontrast, the same factor, EGF, exerted a distinct action on pallidal GABA neurons; itelevated the excitability of these neurons and enabled those to release more amounts ofGABA in the target region. Therefore, these findings suggest that GABAergic neurons inthe brain harbor dynamic plasticity to react with EGF-like factors but the direction andmagnitude of the phenotypic responses differ significantly depending on individualsubtypes of GABAergic neurons.
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