PSA-NCAM is required for activity-induced synaptic plasticity

Neuron. 1996 Sep;17(3):413-22. doi: 10.1016/s0896-6273(00)80174-9.


Hippocampal organotypic slice cultures maintained 10-20 days in vitro express a high level of the polysialylated embryonic form of neural cell adhesion molecule (NCAM) (PSA-NCAM). Treatment of the cultures with endoneuraminidase-N selectively removed polysialic acid (PSA) from NCAM and completely prevented induction of long-term potentiation (LTP) and long-term depression (LTD) without affecting cellular or synaptic parameters. Similarly, slices prepared from transgenic mice lacking the NCAM gene exhibited a decaying LTP. No inhibition of N-methyl-D-aspartic acid receptor-dependent synaptic responses was detected. Washout of the enzyme resulted in reexpression of PSA immunoreactivity which correlated with a complete recovery of LTP and LTD. This reexpression was blocked by TTX and low calcium and enhanced by bicuculline. Taken together, these results indicate that neuronal activity regulates the expression of PSA-NCAM at the synapse and that this expression is required for the induction of synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Electrophysiology
  • Glycoside Hydrolases / pharmacology
  • Hippocampus / chemistry
  • Hippocampus / physiology
  • Immunohistochemistry
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Immunoelectron
  • N-Acetylneuraminic Acid / analysis
  • N-Acetylneuraminic Acid / physiology*
  • Neural Cell Adhesion Molecules / analysis
  • Neural Cell Adhesion Molecules / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / chemistry
  • Synapses / physiology
  • Synapses / ultrastructure


  • Neural Cell Adhesion Molecules
  • Receptors, N-Methyl-D-Aspartate
  • Glycoside Hydrolases
  • endo-alpha-sialidase
  • N-Acetylneuraminic Acid