NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity

Cereb Cortex. 2016 Apr;26(4):1804-17. doi: 10.1093/cercor/bhw007. Epub 2016 Feb 2.


Nogo receptor 1 (NgR1) is expressed in forebrain neurons and mediates nerve growth inhibition in response to Nogo and other ligands. Neuronal activity downregulates NgR1 and the inability to downregulate NgR1 impairs long-term memory. We investigated behavior in a serial behavioral paradigm in mice that overexpress or lack NgR1, finding impaired locomotor behavior and recognition memory in mice lacking NgR1 and impaired sequential spatial learning in NgR1 overexpressing mice. We also investigated a role for NgR1 in drug-mediated sensitization and found that repeated cocaine exposure caused stronger locomotor responses but limited development of stereotypies in NgR1 overexpressing mice. This suggests that NgR1-regulated synaptic plasticity is needed to develop stereotypies. Ex vivo magnetic resonance imaging and diffusion tensor imaging analyses of NgR1 overexpressing brains did not reveal any major alterations. NgR1 overexpression resulted in significantly reduced density of mature spines and dendritic complexity. NgR1 overexpression also altered cocaine-induced effects on spine plasticity. Our results show that NgR1 is a negative regulator of both structural synaptic plasticity and dendritic complexity in a brain region-specific manner, and highlight anterior cingulate cortex as a key area for memory-related plasticity.

Keywords: NgR1; cocaine sensitization; dendritic structure; spatial memory; spine plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cocaine / administration & dosage
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Diffusion Tensor Imaging
  • Female
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism
  • Locomotion* / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity* / drug effects
  • Nogo Receptor 1 / genetics
  • Nogo Receptor 1 / metabolism*
  • Recognition, Psychology / physiology*
  • Rotarod Performance Test
  • Spatial Learning / physiology*


  • Nogo Receptor 1
  • Rtn4r protein, mouse
  • Cocaine