A role of RPTP in fear memory formation and methamphetamine addiction

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: National Institute for Basic Biology
• Principal Investigator: FUJIKAWA Akihiro 基礎生物学研究所, 統合神経生物学研究部門, 特別協力研究員 (50414016)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: チロシンリン酸化 / チロシンホスファターゼ / 覚せい剤 / 記憶 / シナプス

Outline of Final Research Achievements

The objective of this study was to determine the signaling pathway in which PTPRZ, a receptor-type tyrosine phosphates, enhances context fear memory formation, and methamphetamine-induced place preference. We found that phosphorylation of GIT1 at tyrosine residue 554 was higher in the synaptosomes obtained from Ptprz-deficient mice than in those from wild-type mice. We also revealed that GIT1 dephosphorylation by PTPRZ was essential for the normal GIT1 function. These new findings suggest that the regulation of GIT1 by PTPRZ in central synapses leads to undesirable learning outcomes in the fear memory consolidation (the animal model of post-traumatic stress disorder), and drug addiction. Unfortunately, we failed to develop a cell permeable pseudosubstrate PTPRZ inhibitor, and therefore the in vivo effect of pharmacological PTPRZ inhibition could not be examined.

Free Research Field

脳神経科学全般