Figure 7. Synopsis of progressively abnormal synaptic signaling in old A53T-SNCA striata.

This schematic illustration summarizes the progressive pathology of a striatal MSN dendritic spine. The MSN is innervated by nigrostriatal dopaminergic input where the presence of pathogenic overexpressed A53T-SNCA causes elevated presynaptic DA. In glia cells, the DA degradation enzyme COMT is transcriptionally downregulated, suggesting altered extracellular turnover of DA. Postsynaptically, the upregulation of DRD1A and DRD2 and the decreased transcript levels of several DA-inducible genes suggest a progressively diminishing striatal DA response. In parallel, the plasticity of corticostriatal glutamatergic synapses is affected through retrograde signaling, leading to the absence of LTD.