Late loss of connections during callosal development in Siamese cats

Siamese cats are hypopigmented mutants which have abnormal retino-geniculo-cortical pathways. The callosal pathway between areas 17 and 18 of the two cortical hemispheres also exhibits abnormalities: projections arising from the supragranular layers are more widely distributed but greatly reduced in number compared to normally pigmented (NP) cats, whereas those from the infragranular layers are more widespread and more numerous than normal (Berman and Grant, Visual Sci., 9 (1992). Here we examine the development of these abnormalities, using pathway tracing combined with quantitative analyses of the projection in normal and Siamese kittens at different postnatal ages. In neonatal kittens of both strains studied prior to natural eye-opening supragranular layer callosal projections arose throughout areas 17 and 18, with those from the infragranular layers restricted more to the region of the area 17/18 border. Between postnatal days 10 and 30 there was a similar, major (approximately 50%) reduction in the number and distribution of supragranular layer callosal projections from the two areas. The reductions in the normal kittens largely established the adult pattern of projection, but in the Siamese kittens twice as many callosal neurons were present than in adults of the mutant genotype and this situation persisted at the end of the second postnatal month. There was also a major (> or = 50%) reduction in the number and distribution of infragranular layer callosal projections in the NP kittens after eye-opening, but in the mutants such reductions did not occur. Thus the sequence of callosal development in the Siamese cat differs markedly for its two laminar components and by comparison with normal animals: an abnormally late loss of the main source of callosal projections occurs from the upper cortical layers, while the lower layers maintain an early exuberancy. We conclude that abnormal callosal connectivity in these mutants does not result from a misrouting of growing callosal axons, but from subsequent alterations to different mechanisms of cortical pathway development.