Aberrant trajectory of entorhino-dentate axons in the mutant Shaking Rat Kawasaki: a Dil-labelling study

The Shaking Rat Kawasaki (SRK) is a neurological mutant that exhibits abnormalities of cell migration and lamination, with many similarities to the mouse reeler mutant. We recently used lamina-specific antibody staining to show that despite severe aberrations in the laminar organization of the SRK dentate gyrus, the entorhinal terminal field in the outer dentate molecular layer appeared relatively normal (Woodhams & Terashima, 1999, J. Comp. Neurol. 409 p57). However, neurofilament immunostaining suggested that entorhino-dentate afferents take an abnormal trajectory in reaching their appropriate targets, the granule cells dendrites. In the present study, anterograde tracing with the carbocyanine dye 1, 1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) has been used to delineate directly the path that entorhinal axons take to the dentate gyrus, confirming that in SRK entorhinal axons do indeed reach their appropriate terminal fields in the molecular layer, with laminar segregation between projections from the lateral and medial entorhinal cortices. However, these fibres fail to cross the hippocampal fissure between the subiculum and the dentate gyrus, coursing instead parallel to it until they curve round the deepest point of the fissure in field CA3. Similar findings were seen in the murine reeler mutant. Insertion of DiI crystals into the entorhinal cortex of neonatal rats also retrogradely labelled the developmentally transient Cajal-Retzius cells at the hippocampal fissure; these survive for longer in SRK than in normal littermates. The presence of a marked astrogliosis at the SRK hippocampal fissure may play a part in determining the abnormal trajectory taken by entorhino-dentate afferents in this mutant.