Region-specific expression patterns of human α-Synuclein versus murine Synuclein in neocortical and hippocampal areas. Coronal (A) and sagittal (B) overview images demonstrate that transgenic expression of hα-Syn (green channel) is most prominent in the cerebral cortex (RSC, S1, Pir, CA1-3, M2, oCx), subcortical telencephalic structures (AMY, CPu, NAc, Olf), medial thalamic nuclei (mTh), the arcuate hypothalamic nucleus (AHN), and the pontine nucleus (PN) in transgenic mice. Please note that expression in the hippocampal formation (HC) is restricted to CA1-3 but is largely absent from dentate gyrus (DG) (A). In contrast, using antibodies directed against either (A) a species-independent N-terminal epitope of N-α/β-Syn or (B) a species-independent epitope of pan α-Syn shows expression throughout most areas of the brain including subcortical structures (red channel). Higher magnification reveals accumulation of transgenic hα-Syn in a subset of cells (arrows) in the stratum pyramidale (sp) of hippocampal CA3 (C) and in cortical layers V-VI (D). Neuropil in strata oriens (so) and radiatum (sr) shows high hα-Syn immunoreactivity, which in contrast is mostly absent arrowheads from strata lucidum (sl) and lacunosum moleculare (slm) (C). In non-transgenic mice, hippocampal expression of murine α/β-Syn (E) is restricted to mossy fiber terminals in stratum lucidum (arrowheads) but is absent from neuronal somata, whereas in the neocortex (F) some cells close to white matter (wm) are α/β-Syn positive arrows. Please note the specificity of the antibody directed against the human isoform of α-Syn, as evident from absence of immunoreactivity on non-transgenic tissue (green channel in E, F
). Scale bar: 2 mm (A, B), 150 μm (C-F). Abbreviations: amygdala (AMY), cerebellum (Cb), cornu ammonis areas 1–3 (CA1-3), caudate/putamen (CPu), motor cortex (M2), nucleus accumbens (NAc), orbital frontal cortex (oCx), olfactory bulb (Olf), piriform cortex (Pir), retrosplenial cortex (RSC), somatosensory cortex (S1), thalamus (Th).