Figure 3

Mossy fiber presynapse morphology is altered because of Tau ^RDΔ expression. (a) Microphotograph depicting an example of an acute, horizontal slice preparation shot with DiI coated gold particles (red arrow) to obtain neuronal membrane staining. Hippocampal sub-regions dentate gyrus (DG), CA3 and CA1 are visible. (b) Higher magnification of region of interest marked in (a) (white square) located in stratum lucidum of area CA3. Characteristic structural, postsynaptic features of CA3 pyramidal neurons are highlighted (thorny excrescences (th.ex.), orange arrow). Moreover, mossy fiber axons with boutons and filopodia are visible and correspond to the criteria for bouton selection (red arrow = filopodium; white arrow = bouton body). (c) Immunohistological detection of conformation altered Tau with MC-1 antibody in a control littermate mouse at 13 ± 1 month, display no staining. (d) MC-1 immunofluorescence staining in aged matched pro-aggregant mouse (Pro) in s.l. Immunoreactivity is detected. (e) Higher magnification of the indicated region in (d; white square). MC-1 immunostaining revealed immunoreactivity in mossy fiber boutons. (f) Example of a mossy fiber “giant” bouton in control littermate mice (Ctrl). (g) Mossy fiber bouton of a pro-aggregant mouse (Pro) with filopodia emanating from the bouton surface. (h) Area CA3 mossy fiber bouton of an anti-aggregant mouse (Anti). (i) Example of a Tau knockout mouse bouton (TKO). (j) Measurement of bouton diameter in control littermate (black column), pro-aggregant (red column), anti-aggregant (green column) and Tau knockout mice (blue column) illustrating an increase of ~ 45% in diameter in pro-aggregant and Tau knockout mice. (10 slices prepared from at least 3 different animals per group). Error bars = SEM; p-value < 0.001***.