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

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.

Five Hours Total Sleep Deprivation Does Not Affect CA1 Dendritic Length or Spine Density.

Sleep is essential for long term memory function. However, the neuroanatomical consequences of sleep loss are disputed. Sleep deprivation has been reported to cause both decreases and increases of dendritic spine density. Here we use Thy1-GFP expressing transgenic mice to investigate the effects of acute sleep deprivation on the dendritic architecture of hippocampal CA1 pyramidal neurons. We found that 5 h of sleep deprivation had no effect on either dendritic length or dendritic spine density. Our work suggests that no major neuroanatomical changes result from a single episode of sleep deprivation.

Role of Nogo Receptor-1 for Recovery of Balance, Cognition, and Emotion after Mild Traumatic Brain Injury in Mice.

Mild traumatic brain injury (mTBI) constitutes 75 ∼ 90% of all TBI cases and causes various physical, cognitive, emotional, and other psychological symptoms. Nogo receptor 1 (NgR1) is a regulator of structural brain plasticity during development and in adulthood. Here, we used mice that, in the absence of doxycycline, overexpress NgR1 in forebrain neurons (MemoFlex) to determine the role of NgR1 in recovery from mTBI with respect to balance, cognition, memory, and emotion. We compared wild-type (WT), MemoFlex, and MemoFlex + doxycycline mice to the same three groups subjected to mTBI. mTBI was induced by a controlled 30-g weight drop. We found that inability to downregulate NgR1 significantly impairs recovery from mTBI-induced impairments. When the NgR1 transgene was turned off, recovery was similar to that of WT mice. The results suggest that the ability to regulate NgR1 signaling is needed for optimal recovery of motor coordination and balance, spatial memory, cognition, and emotional functions after mTBI.