Where no synapses go: gatekeepers of circuit remodeling and synaptic strength

Trends Neurosci. 2013 Jun;36(6):363-73. doi: 10.1016/j.tins.2013.04.003. Epub 2013 May 2.

Abstract

Growth inhibitory molecules in the adult mammalian central nervous system (CNS) have been implicated in the blocking of axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs), and a key question concerns their physiological role in the naïve CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health.

Publication types

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

MeSH terms

  • Amnesia / physiopathology
  • Animals
  • Astrocytes / physiology
  • Brain / growth & development
  • Brain / physiology
  • Brain Injuries / physiopathology
  • Brain Injuries / therapy
  • Chondroitin Sulfate Proteoglycans / physiology
  • Cytoskeleton / physiology
  • Cytoskeleton / ultrastructure
  • Dendrites / physiology
  • Dendrites / ultrastructure
  • Dominance, Ocular / physiology
  • GPI-Linked Proteins / physiology
  • Glycosaminoglycans / physiology
  • Humans
  • Mental Disorders / physiopathology
  • Mice
  • Models, Neurological
  • Myelin Proteins / physiology
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins / physiology*
  • Neuronal Plasticity / physiology*
  • Nogo Proteins
  • Nogo Receptor 1
  • Receptors, Cell Surface / physiology
  • Signal Transduction / physiology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy
  • Synapses / physiology*

Substances

  • Chondroitin Sulfate Proteoglycans
  • GPI-Linked Proteins
  • Glycosaminoglycans
  • Myelin Proteins
  • Nerve Tissue Proteins
  • Nogo Proteins
  • Nogo Receptor 1
  • OMG protein, human
  • RTN4 protein, human
  • RTN4R protein, human
  • Receptors, Cell Surface
  • Rtn4 protein, mouse