2013 Fiscal Year Final Research Report
Pathophysiological alterations of intrinsic properties and neural activity in the midbrain dopaminergic neurons mediated by neurotrophic factors
| Project/Area Number |
23500464
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
NAWA Hiroyuki 新潟大学, 脳研究所, 教授 (50183083)
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| Project Period (FY) |
2011 – 2013
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| Keywords | ドパミン / 神経栄養因子 / ニューレグリン / 上皮成長因子 / スパイク発火特性 / 動物モデル / 統合失調症 |
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| Research Abstract |
Neuregulin (NRG) and epidermal growth factor (EGF) have nerurotrophic activities on the midbrain dopaminergic neurons. These factors are implicated with the etiology of neuropsychiatric diseases, such as schizophrenia. NRG/EGF administered rodents during neonatal period exhibit behavioral abnormalities related with schizophrenia. Therefore, these animals are useful models to analyze the neuronal mechanisms underlying the pathophysiology. Slice patch-clamp analyzes of the dopaminergic neurons reveal that NRG or EGF attenuated synaptic inhibition or spike after-hyperpolarization mediated by a certain potassium current, respectively, both of which potentially enhance neural activity. In support of this, in vivo burst firing activity was enhanced under anesthetic condition in NRG or EGF administered animals. Thus, pathophysiological alterations of neuronal properties might participate in abnormal dopaminergic transmission and behavioral traits in the animal models for schizophrenia.
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