alpha-Synuclein produces a long-lasting increase in neurotransmitter release

EMBO J. 2004 Nov 10;23(22):4506-16. doi: 10.1038/sj.emboj.7600451. Epub 2004 Oct 28.


Wild-type alpha-synuclein, a protein of unknown function, has received much attention because of its involvement in a series of diseases that are known as synucleinopathies. We find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of alpha-synuclein clusters. Conversely, suppression of alpha-synuclein expression through antisense nucleotide and knockout techniques blocks the potentiation, as well as the glutamate-induced increase in presynaptic functional bouton number. Consistent with these findings, alpha-synuclein introduction into the presynaptic neuron of a pair of monosynaptically connected cells causes a rapid and long-lasting enhancement of synaptic transmission, and rescues the block of potentiation in alpha-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of alpha-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of alpha-synuclein clusters. Thus, alpha-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cells, Cultured
  • Electrophysiology
  • Endocytosis / drug effects
  • Enzyme Inhibitors / pharmacology
  • Exocytosis / drug effects
  • Hippocampus / cytology
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / ultrastructure
  • Nitric Oxide / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / drug effects
  • Oligonucleotides, Antisense / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synucleins
  • alpha-Synuclein


  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Oligonucleotides, Antisense
  • Recombinant Fusion Proteins
  • Snca protein, mouse
  • Snca protein, rat
  • Synucleins
  • alpha-Synuclein
  • Nitric Oxide
  • Nitric Oxide Synthase