α-synuclein produces a long-lasting increase in neurotransmitter release

Shumin Liu, Ipe Ninan, Irina Antonova, Fortunato Battaglia, Fabrizio Trinchese, Archana Narasanna, Nikolai Kolodilov, William Dauer, Robert D. Hawkins, Ottavio Arancio

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Wild-type α-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 α-synuclein clusters. Conversely, suppression of α-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, α-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 α-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of α-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of α-synuclein clusters. Thus, α-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal.

Original languageEnglish (US)
Pages (from-to)4506-4516
Number of pages11
JournalEMBO Journal
Volume23
Issue number22
DOIs
StatePublished - Nov 10 2004
Externally publishedYes

Keywords

  • Plasticity
  • Synapse
  • Synuclein
  • Terminal

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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