Corticospinal tract neurons are radially malpositioned in the sensory-motor cortex of the Shaking rat Kawasaki.

Shaking rat Kawasaki (SRK) is an autosomal recessive mutant rat that exhibits tremor, dystonia, and ataxia and that is characterized by abnormal lamination of the cerebral and cerebellar cortices and the hippocampus. To examine whether or not layer V neurons in the mutant neocortex are malpositioned in accordance with the aberrant laminar cytoarchitecture, horseradish peroxidase (HRP) was injected into the lumbar spinal cord of SRK mutant and normal control rats to label cortical pyramids projecting through the corticospinal tract (CST). HRP-labeled CST neurons of both normal and SRK rats were found mainly in the hindlimb area of the sensory-motor cortex, indicating a normal tangential distribution of labeled CST neurons in the SRK mutant. In the radial axis, however, labeled CST neurons were spread throughout all layers of the mutant cortex, whereas those in normal rats were restricted to layer V. In the mutant, most labeled CST neurons located in the inner third of the cortex had a typical pyramidal form with an upright apical dendrite, but many of those located near the pial surface displayed abnormal shapes and could be subdivided into inverted pyramidal, horizontal, and bipolar neurons on the basis of their dendritic morphology. The abnormal distribution pattern of labeled CST neurons in the mutant was quantified using a standardized measure of their depth distribution, where 0% = the level of the white matter and 100% = the pial surface. The mean value for the SRK cortex of 47.0% was significantly greater than the figure of 40.5% for normal rats (P < 0.01, Student's t test), indicating a spread of CST neurons toward the pial surface in SRK, but even more striking was the size of the standard deviation: 30.4 in SRK compared with 7.1 in controls. The distribution pattern of CST neurons of the SRK rat was also statistically identical with that of the reeler mouse, which is a well-known mutant that also exhibits an abnormal lamination pattern in the cerebral cortex. These results indicate that neuronal components of the neocortex of the SRK mutant are intermingled along the radial axis, but not in the tangential axis, and provide further evidence for a strong similarity between this spontaneous rat mutation and the reeler malformation.