LATE LOSS OF CONNECTIONS DURING CALLOSAL DEVELOPMENT IN SIAMESE CATS

Siamese cats are hypopigmented mutants which have abnormal retino-geni culo-cortical pathways. The callosal pathway between areas 17 and 18 o f the two cortical hemispheres also exhibits abnormalities: projection s arising from the supragranular layers are more widely distributed bu t greatly reduced in number compared to normally pigmented (NP) cats, whereas those from the infragranular layers are more widespread and mo re numerous than normal (Berman and Grant, Visual Sci., 9 (1992) 1-19) . Here we examine the development of these abnormalities, using pathwa y tracing combined with quantitative analyses of the projection in nor mal and Siamese kittens at different postnatal ages. In neonatal kitte ns of both strains studied prior to natural eye-opening, supragranular layer callosal projections arose throughout areas 17 and 18, with tho se from the infragranular layers restricted more to the region of the area 17/18 border. Between postnatal days 10 and 30 there was a simila r, major (similar to 50%) reduction in the number and distribution of supragranular layer callosal projections from the two areas. The reduc tions in the normal kittens largely established the adult pattern of p rojection, but in the Siamese kittens twice as many callosal neurons w ere present than in adults of the mutant genotype and this situation p ersisted at the end of the second postnatal month. There was also a ma jor (greater than or equal to 50%) reduction in the number and distrib ution of infragranular layer callosal projections in the NP kittens af ter eye-opening, but in the mutants such reductions did not occur. Thu s the sequence of callosal development in the Siamese cat differs mark edly for its two laminar components and by comparison with normal anim als: an abnormally late loss of the main source of callosal projection s occurs from the upper cortical layers, while the lower layers mainta in an early exuberancy. We conclude that abnormal callosal connectivit y in these mutants does not result from a misrouting of growing callos al axons, but from subsequent alterations to different mechanisms of c ortical pathway development.