Elucidation of molecular/neural mechanisms for memory extinction by inducible and reversible gene expression

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: KISHIMOTO Yasushi 徳島文理大学, 薬学部, 准教授 (90441592)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 瞬目反射条件づけ / 消去 / 内在性カンナビノイド / 代謝型グルタミン酸受容体 / 運動学習 / アルツハイマー病 / プリオン / 加齢発達

Outline of Final Research Achievements

The neural mechanisms of memory extinction were investigated by using pharmacological analysis and various mouse models (inducible and reversible KO mice, Alzheimer's disease (AD) model mice, prion protein KO mice, KO mice of monoacylglycerol lipase (MGL), the major hydrolyzing enzyme of 2-AG, and so on). The main results obtained in the study are summarized in the following points: (i) To determine the sites for extinction of eyeblink memory in the cerebellum, we used mGluR1-conditional KO mice bearing inducible and reversible expression of mGluR1 specifically in cerebellar Purkinje cells (PCs). We found that extinction of eyeblink memory was slightly impaired without mGluR1 in PCs. (ii) MGL KO mice showed impaired extinction of eyeblink memory, though fatty acid amide hydrolase (FAAH) inhibition significantly impaired memory acquisition. (iii) In the AD model mice, the impairment of trace memory acquisition preceded impairment of the memory extinction.

Free Research Field

行動遺伝学