Localization of alpha-synuclein to identified fibers and synapses in the normal mouse brain

Alpha-synuclein is a synaptic associated protein that is found throughout the brain. Although its function is not fully understood, various roles have been proposed, including the mobilization of synaptic vesicles and plasticity. However, interest in this molecule is mainly focused on its role in neurodegenerative diseases such as Parkinson's disease, where it is a major component in cellular inclusions. Although it is widely accepted that alpha-synuclein is distributed to terminals and fibers throughout the brain, the identity of the pathways that contain this protein is not known. To address this issue, we combined immunocytochemistry with anterograde tract-tracing in mouse to identify the projections that are alpha-synuclein immunopositive. We find that it is present in corticostriatal, nigrostriatal and striatonigral terminals. Our data support the concept that alpha-synuclein is normally present in at least some of the terminals of inclusion-forming neurons, but that it is also present in the axonal boutons of neurons that do not apparently accumulate this protein pathologically.