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

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.