Expression of alpha-Synuclein in the mouse retina is confined to inhibitory presynaptic elements

a-Synuclein (a-Syn) is enriched in presynaptic terminals of the central nervous system including the retina and plays a role in the synaptic vesicle cycle and synaptic transmission. Abnormal aggregation of a-Syn is considered to be the main component of the Lewy bodies that are the pathological hallmarks of Parkinson's disease. Although expression pattern of a-Syn has been described in the retinas, its precise cellular and subcellular locations are poorly understood. We investigated the precise expression of a-Syn using light microscopy (LM) and electron microscopy (EM) with antibodies against a-Syn in the mouse retina. We found that the majority of a-Syn immunoreactivity (IR) is located in GABAergic, glycinergic, and dopaminergic amacrine cells, and their processes often make a direct synapse to other labeled or unlabeled amacrine profiles, bipolar cell terminals, or ganglion cell dendrites. Further, our LM and immuno-EM results confirm the absence of a-Syn in excitatory photoreceptors, bipolar cell bodies, and their ribbon synapses, providing evidence, for the first time, that ribbon synapses do not express a-Syn. Additionally, a-Syn IR is located in the ganglion cells, some of which are intrinsically photosensitive retinal ganglion cells. These results reveal a previously unappreciated inhibitory synapse-specific expression pattern of a-Syn in the retina, suggesting that a-Syn may play a distinct role in the modulation and integration of inhibitory synaptic transmission in the retina.