Fig. 3

Ultrastructural study of large swellings seen in the CA1 region of the hippocampus of 12-month-old mice These likely correspond to the large puncta found in the novel clusters labeled with immunofluorescence for NeuN (Fig. 1a–c). All appear to be derived from presynaptic terminals, and they may represent approximately 3 stages in the formation of the swellings. a Stage 1: The swelling in A shows central mitochondria (mito) and large clusters of presynaptic vesicles (arrows) including one cluster at an active zone on a spine synapse (sp). The cytoplasm is dense and full of thick fibrils. B, c Stage 2: The swelling in B and c is filled with thick fibrils but has very few presynaptic vesicles; a group (arrow) can be seen at an active zone of a spine synapse (sp). A–C are from the CA1 stratum radiatum (A, KO; B, C, WT). D–F -Stage 3: Many of the swellings are light with no evident presynaptic vesicles and with thin fibrils. In these 3 examples from the CA1 stratum oriens of a DPP6-KO mouse, the periphery of the swelling is very convoluted, and it extends thin processes around the surrounding synapses (similar in appearance to glial processes). However, in all 3 images, one of the processes from the swelling appears to be continuous with a terminal filled with presynaptic vesicles (arrows). D–F also shows distinctive invaginating presynaptic terminals (arrowheads). Scale bars in A and C are 1 μm, and the one in A is for all other micrographs. ad, apical dendrite of pyramidal neuron