Abstract
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.
Highlights
The reeler mouse is an autosomal recessive mutation and was first described by Falconer (1951), Hamburgh (1963) and later more extensively by Caviness and co-workers (Caviness et al, 1972; Caviness and Sidman, 1973; Pinto-Lord and Caviness, 1979)
More recent studies demonstrated that by binding the two lipoprotein receptors, apolipoprotein E receptor (ApoER2) and very low-density lipoprotein receptor (VLDLR), Reelin interacts with the Notch-pathway, thereby regulating radial migration, polarity and branching of newborn excitatory neurons along radial glial fibers (Borrell et al, 1999; Trommsdorff et al, 1999; Hack et al, 2007; Hashimoto-Torii et al, 2008; Chai et al, 2015, 2016)
Cytoarchitectural Organization of the Adult Reeler Mouse Neocortex. It has been clearly demonstrated by numerous studies that the characteristic six-layered structure of the neocortex including the ‘‘barrel field’’ of the somatosensory area in adult wild type (WT) mice undergoes severe alterations in its cytoarchitecture in the adult reeler mouse neocortex as revealed by Nissl, cytochrome oxidase staining and layer-specific cDNA probes (Caviness et al, 1976; Welt and Steindler, 1977; Wagener et al, 2010, 2016; Cremer et al, 2011)
Summary
The reeler mouse is an autosomal recessive mutation and was first described by Falconer (1951), Hamburgh (1963) and later more extensively by Caviness and co-workers (Caviness et al, 1972; Caviness and Sidman, 1973; Pinto-Lord and Caviness, 1979). Migrating neurons abnormally adhere much stronger to radial glial fibers during the period of neuronal differentiation and growth in reeler (Caviness and Rakic, 1978; Pinto-Lord et al, 1982). More recent studies demonstrated that by binding the two lipoprotein receptors, apolipoprotein E receptor (ApoER2) and very low-density lipoprotein receptor (VLDLR), Reelin interacts with the Notch-pathway, thereby regulating radial migration, polarity and branching of newborn excitatory neurons along radial glial fibers (Borrell et al, 1999; Trommsdorff et al, 1999; Hack et al, 2007; Hashimoto-Torii et al, 2008; Chai et al, 2015, 2016). Various other anatomical anomalies were described in a number of different CNS areas in reeler (reviewed by Katsuyama and Terashima, 2009)
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