title: Nogo receptor 1 regulates formation of lasting memories.
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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Karlén
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Karlsson
authors.forename: Anna
authors.initials: A
authors.lastname: Mattsson
authors.forename: Karin
authors.initials: K
authors.lastname: Lundströmer
authors.forename: Simone
authors.initials: S
authors.lastname: Codeluppi
authors.forename: Therese M
authors.initials: TM
authors.lastname: Pham
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Bäckman
authors.forename: Sven Ove
authors.initials: SO
authors.lastname: Ogren
authors.forename: Elin
authors.initials: E
authors.lastname: Aberg
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Hoffman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sherling
authors.forename: Carl R
authors.initials: CR
authors.lastname: Lupica
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Hoffer
authors.forename: Christian
authors.initials: C
authors.lastname: Spenger
authors.forename: Anna
authors.initials: A
authors.lastname: Josephson
authors.forename: Stefan
authors.initials: S
authors.lastname: Brené
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000070798:Nogo Proteins; D016548:Prosencephalon / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D045442:Rotarod Performance Test; D019076:Transgenes / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C523678:LINGO1 protein, mouse; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D018124:Receptors, Tumor Necrosis Factor; C000603201:Rtn4 protein, mouse; C409471:Tnfrsf19 protein, mouse