Nogo receptor 1 regulates formation of lasting memories |
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| Authors: | Alexandra Karlén Tobias E. Karlsson Anna Mattsson Karin Lundstr?mer Simone Codeluppi Therese M. Pham Cristina M. B?ckman Sven Ove ?gren Elin ?berg Alexander F. Hoffman Michael A. Sherling Carl R. Lupica Barry J. Hoffer Christian Spenger Anna Josephson Stefan Brené Lars Olson |
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| Affiliation: | aDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden; ;bDepartment of Neurobiology, Caring Sciences and Society, and ;dDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86 Stockholm, Sweden; and ;cNational Institute on Drug Abuse, National Institutes of Health, 251 Bayview Dr., Baltimore, MD 21224 |
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| Abstract: | 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 rearrangements that carry lasting memories may facilitate development of treatments for memory dysfunction. |
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| Keywords: | behavior hippocampus long-term potentiation myelin inhibitors synaptic plasticity |
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