期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 48, 页码 20476-20481出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0905390106
关键词
behavior; hippocampus; long-term potentiation; myelin inhibitors; synaptic plasticity
资金
- Swedish Medical Research Council, Torsten
- Ragnar Soderberg's Foundation
- Swedish Brain Foundation
- Hallsten Foundation
- Swedish Brain Power
- AFA (Arbetsmarknadens forsakringsaktiebolag) Sweden
- U. S. Public Health Service
- National Institute on Drug Abuse
- National Institutes of Health
- Karolinska Institute
Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests. Blocking transgene expression normalizes these memory impairments. Nogo, Lingo-1, Troy, endogenous NgR1, and BDNF mRNA expression levels were not altered by transgene expression, suggesting that the impaired ability to form lasting memories is directly coupled to inability to down-regulate NgR1. Regulation of NgR1 may therefore serve as a key regulator of memory consolidation. Understanding the molecular underpinnings of synaptic re-arrangements that carry lasting memories may facilitate development of treatments for memory dysfunction.
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