Role of islands of Calleha in anhedonia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19459
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Aizawa Hidenori 広島大学, 医系科学研究科(医), 教授 (80391837)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: カレハ島 / 腹側線条体 / ドーパミン / うつ病 / アンヘドニア

Outline of Final Research Achievements

Abstract of the current study is summarized as follows. 1. Histological analysis revealed that mouse ventral striatum included the islands of Calleja expressing Gad67 mRNA, NeuN-positive GABAergic neurons. 2. A novel behavioral system for quantitative measurement of anhedonia-like behaviors was developed for mice. Specifically, sequential sweep of the descending stimulation frequencies for the intracranial self-stimulation upon nose poking of the port in the operant chamber enabled the quantification of the behavioral measure useful for anhedonia-like behaviors. Indeed, antidepressant nomifensine decreased significantly threshold for the hedonic behavior revealed by the current methods. 3. Gene expression sets specific to the murine islands of Calleja was established by applying immunoprecipitation and RNA-seq analyses to the mouse line expressing ribosomal protein-GFP fusion protein specifically in the islands of Calleja.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

「楽しい」と感じなくなる無快楽症（アンヘドニア）は、うつ病の診断基準に含まれるうつ病のコア症状である。また、日常生活での喜びや興味、生きがいに快楽情動は不可欠であり、その喪失はうつ病患者のQOLを著しく損ねる。この問題に取り組む上で、分子的解析を可能にする動物実験が不可欠であるが、アンヘドニアの病態モデルや定量的解析は研究伸展が不十分である。本研究は、アンヘドニアの基盤として腹側線条体の機能異常に注目し、その解剖学知見を明らかにするとともに、新たなアンヘドニア検証系を開発する点で意義深い。