Quantitative Three-Dimensional Reconstructions of Excitatory Synaptic Boutons in the "Barrel Field" of the Adult "Reeler" Mouse Somatosensory Neocortex: A Comparative Fine-Scale Electron Microscopic Analysis with the Wild Type Mouse.

Synapses are key structural determinants for information processing and computations in the normal and pathologically altered brain. Here, the quantitative morphology of excitatory synaptic boutons in the "reeler" mutant, a model system for various neurological disorders, was investigated and compared with wild-type (WT) mice using high-resolution, fine-scale electron microscopy (EM) and quantitative three-dimensional (3D) models of synaptic boutons. Beside their overall geometry, the shape and size of presynaptic active zones (PreAZs) and postsynaptic densities (PSDs) forming the active zones and the three pools of synaptic vesicles (SVs), namely the readily releasable pool (RRP), the recycling pool (RP), and the resting pool, were quantified. Although the reeler mouse neocortex is severely disturbed, no significant differences were found in most of the structural parameters investigated: the size of boutons (~3 µm2), size of the PreAZs and PSDs (~0.17 µm2), total number of SVs, and SVs within a perimeter (p) of 10 nm and p20 nm RRP; the p60 nm, p100 nm, and p60-p200 nm RP; and the resting pool, except the synaptic cleft width. Taken together, the synaptic organization and structural composition of synaptic boutons in the reeler neocortex remain comparably "normal" and may thus contribute to a "correct" wiring of neurons within the reeler cortical network.

Structural and Synaptic Organization of the Adult Reeler Mouse Somatosensory Neocortex: A Comparative Fine-Scale Electron Microscopic Study of Reeler With Wild Type Mice.

The reeler mouse has been widely used to study various aspects of cortico- and synaptogenesis, but also as a model for several neurological and neurodegenerative disorders. In contrast to development, comparably little is known about the neuronal composition and synaptic organization of the adult reeler mouse neocortex, in particular at the fine-scale electron microscopic level, which was investigated here and compared with wild type (WT) mice. In this study, the "barrel field" of the adult reeler and WT mouse somatosensory neocortex is used as a model system. In reeler the characteristic six-layered structure is no longer existent, but replaced by a conglomerate of neurons organized in homologous clusters with maintained morphological identity and heterologous clusters between neurons and/or oligodendrocytes. These clusters are loosely scattered throughout the neocortical mass between the pial surface and the white matter. In contrast to WT, layer 1 (L1), if existent, seems to be diluted into the volume of the neocortical mass with no clear boundary. L1 also contains clusters of migrated or persistent neurons, oligodendro- and astrocytes. As in WT, myelinated and unmyelinated axons were found throughout the neocortical mass, but in reeler they were organized in massive fiber bundles with a high fiber packing density. A prominent and massive thalamocortical projection traverses through the neocortical mass, always accompanied by numerous "active" oligodendrocytes whereas in WT no such projections were found and "silent" oligodendrocytes were restricted to the white matter. In the adult reeler mouse neocortex, synaptic boutons terminate on somata, dendritic shafts, spines of different types and axon initial segments with no signs of structural distortion and/or degeneration, indicating a "normal" postsynaptic innervation pattern of neurons. In addition, synaptic complexes between boutons and their postsynaptic targets are tightly ensheathed by fine astrocytic processes, as in WT. In conclusion, the neuronal clusters may represent a possible alternative organization principle in adult reeler mice "replacing" layer formation. If so, these homologous clusters may represent individual "functional units" where neurons are highly interconnected and may function as the equivalent of neurons integrated in a cortical layer. The structural composition and postsynaptic innervation pattern of neurons by synaptic boutons provide the structural basis for the establishment of a functional although altered cortical network in the adult reeler mouse.