Open AccessNogo receptor 1 regulates formation of lasting memories
Author(s) -
Alexandra Karlén,
Tobias E. Karlsson,
Anna Mattsson,
Karin Lundströmer,
Simone Codeluppi,
T. M. Pham,
Cristina M. Bäckman,
Sven Ove Ögren,
Elin Åberg,
Alexander F. Hoffman,
Michael A. Sherling,
Carl R. Lupica,
Barry J. Hoffer,
Christian Spenger,
Anna Josephson,
Stefan Brené,
Lar̀s Olson
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0905390106
Subject(s) - long term potentiation , forebrain , memory consolidation , neuroscience , transgene , impaired memory , regulator , endogeny , genetically modified mouse , psychology , receptor , hippocampus , biology , central nervous system , cognition , endocrinology , gene , biochemistry
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.