Nogo receptor 1 regulates formation of lasting memories.
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.
Karlén
Alexandra
A
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
Karlsson
Tobias E
TE
Mattsson
Anna
A
Lundströmer
Karin
K
Codeluppi
Simone
S
Pham
Therese M
TM
Bäckman
Cristina M
CM
Ogren
Sven Ove
SO
Aberg
Elin
E
Hoffman
Alexander F
AF
Sherling
Michael A
MA
Lupica
Carl R
CR
Hoffer
Barry J
BJ
Spenger
Christian
C
Josephson
Anna
A
Brené
Stefan
S
Olson
Lars
L
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
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