Transgenic lines expressing human disease proteins that show axonal transport defects also show abnormalities in synaptic morphology.

<p><b>A:</b> Larval segmental nerves from wild type larvae show smooth staining with the synaptic vesicle marker CSP. Pre (HRP-green) or post synapses (DLG-red) are clearly observed in these larval NMJs. Bar = 10 µm and 20 µm. <b>B:</b> Segmental nerves from larvae expressing human APPswe show axonal blockages similar to previous observations (arrows) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104617#pone.0104617-Gunawardena3" target="_blank">[63]</a>. Both pre (HRP, green) and post synaptic markers (DLG, red) show synaptic morphology defects. Note that the post synaptic area (red) is much greater than what is observed in wild type in the enlarged image (arrow). <b>C:</b> Segmental nerves from larvae expressing pathogenic polyQ77 show axonal blockages similar to previous observations (arrows) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104617#pone.0104617-Gunawardena5" target="_blank">[97]</a>. Pre (HRP, green) and post synaptic (DLG, red) markers show synaptic morphology defects. Note that the post synaptic areas (red) is much great than what is observed in wild type (arrow) in the enlarged image. <b>D:</b> Quantitative analysis did not show any significant changes in the average number of parent boutons in larvae expressing APPswe (p = 0.320) or polyQ77 (p = 0.326) compared to wild type. Y axis is the average number of parent boutons. <b>E:</b> Quantitative analysis of the percent of satellite boutons shows a significant increase in larvae expressing APPswe compared to wild type (p = 0.0069), while larvae expressing polyQ77 are similar to wild type (p = 0.193). Y axis is the percent of satellite boutons. <b>F:</b> The total number of boutons are significantly increased in larvae expressing APPswe (p = 0.0101), while no significant change is seen in larvae expressing polyQ77 compared to wild type (p = 0.277). The increase in the total number of boutons in larvae expressing APPswe is the result of an increase in the number of satellite boutons. Y axis is the total number of boutons. <b>G:</b> Quantitative analysis of synaptic bouton area reveals a significant reduction in the pre-synaptic bouton areas of APPswe larvae (p = 0.0468) compared to wild type. These defects are similar to what was seen in khc−/− larvae (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104617#pone-0104617-g001" target="_blank">Figure 1G</a>). The pre synaptic bouton areas from larvae expressing polyQ77 are similar to wild type (p = 0.9886). Y axis is the pre synaptic area µm2. While a significant reduction is not observed in the post synaptic bouton areas in APPswe larvae (p = 0.12), a significant increase in the post synaptic boutons areas is seen in polyQ77 (p = 0.018) larvae compared to wild type. Y axis is the pre synaptic area µm2. H: A significant decrease is seen in the synaptic length in APPswe larvae (p = 0.00024), similar to roblk−/− NMJs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104617#pone-0104617-g001" target="_blank">Figure 1</a>), while polyQ77 larvae are similar to wild type (p = 0.133). Y axis = average synaptic length (µm). 10 larvae were imaged and analyzed to evaluate axonal transport and synaptic defects. For statistical analysis ANOVA was used followed by post-hoc analysis using the Bonferroni's test.