Topography of interhemispheric connections in neocortex of mice with congenital deficiencies of the callosal commissure

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Abstract
Normally, axons within the corpus callosum are ordered according to the cortical regions from which they originate, and callosal cells and terminations form elaborate cortical patterns related to the underlying topographic representations of the sensory periphery. About 30% of mice of the BALB/c strain show congenital deficiencies of the callosal commissure which range from total absence of the corpus callosum to a moderate reduction in the size of this commissure. In the light of current theories about the origin of these callosal deficiencies, it seems likely that fibers crossing the mid‐plane in mutant mice have to circumvent local disturbances along their migration path. Since these disturbances in fiber trajectory may, in turn, alter the overall pattern of callosal projections, we set out to investigate whether the distribution of callosal connections in mice with marked deficiencies of the corpus callosum is as ordered as in normal mice. In groups of normal and mutant mice, we used multiple injections of horseradish peroxidase to reveal the overall distribution of callosal connections and restricted injections of horseradish peroxidase conjugated with wheat germ agglutinin to reveal finer aspects of the organization of the callosal pathway in these animals. Our results show that the number of labeled cells is reduced in mice with a small corpus callosum and that no labeled cells are present in the neocortex of acallosal mice. Furthermore, the topographic distribution of fibers within the corpus callosum of mutant mice can be significantly less ordered than in normal mice. However, even in mice with extreme deficiencies of the corpus callosum, callosal fibers originate from and terminate in all major areas of the cortex, and, within these areas, callosal cells and terminations are distributed according to the normal plan. The laminar distribution of callosal cells also appears normal in these mice. These findings indicate that gross developmental anomalies of the corpus callosum do not prevent normal specification of the callosal pattern during development. Within the context of current theories about the origin of congenital callosal deficiencies, our findings suggest that callosal fibers are able to establish appropriate contralateral connections in spite of alterations of their migration route. They also suggest that fiber topography within the corpus callosum does not play an important role in guiding migrating axons to their correct contralateral targets. Finally, our failure to find labeled fibers within the anterior commissure indicates that this commissure does not serve as an alternative route for deviated callosal axons.