Basal activity and sensory responses of nigral dopamine neuron in awake state of rodent model for schizophrenia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06868
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Niigata University
• Principal Investigator: Namba Hisaaki 新潟大学, 脳研究所, 助教 (90332650)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ドパミン / モデル動物 / 覚醒記録 / 聴覚応答

Outline of Final Research Achievements

Epidermal growth factor (EGF) has neurotrophic effects on the developing dopaminergic neurons. Administered animals with EGF as neonate exhibit behavioral abnormalities related with schizophrenia in adulthood. As “dopamine hypothesis” is so far proposed as a hypothesis of schizophrenia, abnormal dopaminergic transmission could be related with pathophysiology. However, actual dopaminergic activity in awake state were not so far determined in this model animals, which might be related with symptoms, such as auditory hallucination. Analyses of basal activity in awake state reveal marked enhancement in the mice model. In addition, this enhancement affects auditory responses evoked by pure tone stimulation with rather higher frequency. Especially, the level of transient increase in the frequency during offset period was markedly enhanced in EGF-treated mice. Thus, these aberrant activity of dopamine neurons could be pathophysiology of this animal model.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

統合失調症は、幻覚や妄想などが伴う重篤な精神疾患であり、いまだ根治するための有効な治療法は見いだされていない。そのため疾患脳病態や発症のメカニズムの解明は、新たな治療薬開発のための治療標的の発見にもつながるものと考えられる。本研究は、疾患モデル動物のサイトカイン異常によって障害されるドパミン機能に着目して解析することで、疾患症状に関連する脳病態を明らかにしようとしたものであり、その成果は、疾患症状にかかわる神経回路機能異常やそれを引き起こす分子機序の解明につながるものと考えられる。