Objective: Alpha-synuclein is a major key player in Parkinson’s disease, however its physiological function still remains elusive. Using super-resolution microscopy this study aims to analyse the spatial distribution of alpha-synuclein within the pre-synaptic terminal upon neuronal stimulation.

Background: Conventional microscopy is limited by light diffraction and thereby a maximum resolution of 200 nm can be achieved. Super-resolution microscopy permits a resolution of around 10-20 nm and thus a detailed insight into a synapse with a size of 500 nm to 1 µm.

Methods: To study synaptic localization we prepared synaptosomes, ‘pinched-off and resealed nerve endings’ from adult rat brain. Alpha-synuclein and specific synaptic proteins were stained and imaged by direct stochastic optical reconstruction microscopy (dSTORM).

Results: Interestingly, we observed a highly specific localization of alpha-synuclein at the active zone of the pre-synaptic terminal upon treatment of synaptosomes with KCl and Ca2+, whereas synaptobrevin positive vesicles were localized throughout the synaptosomes, even upon stimulation. Alpha-synuclein was never found across the whole population of synaptic vesicles, unlike synaptotagmin and synaptobrevin, even in the absence of KCl and Ca2+ stimulation.

Conclusions: This study shows for the first time that alpha-synuclein is not uniformly distributed within the pre-synaptic terminal. Thus, its colocalization with the active zone may emphasize its possible role in fusion and reuptake of synaptic vesicles.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-super-resolution-microscopy-reveals-potential-new-role-of-alpha-synuclein-at-the-pre-synapse/