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Abstract:Relatively few behavioral deficits are apparent in subjects with hereditary absence of the corpus callosum (CC). The anterior commissure (AC) has been suggested to provide an extracallosal route for the transfer of interhemispheric information in subjects with this congenital defect. Anterior commissure size, axon number, axon diameter, and neuronal distribution were compared between normal mice and those with complete CC absence. No difference in midsagittal AC area was found between normals and acallosals, nor were differences found in the numbers or diameters of myelinated axons. However, axon counts indicated an 17%increase or about 70,000 more unmyelinated axons in the AC of acallosal mice, and the mean diameter of unmyelinated axons was slightly less than in normal mice (0.24 vs 0.26 μm). This decrease in axon diameter enabled more axons to pass through the AC without increasing its midsagittal area. The topographical distribution of neurons sending axons through the AC, assessed with lipophilic dyes, was qualitatively similar for almost all the known regions of origin of the anterior commissure in normal and acallosal mice. There was a pronounced deficit of AC cells in the anterior piriform cortex of BALB/c mice, but this occurred whether or not the mouse suffered absent CC. Although the increase in AC axon number is far smaller than the number of CC axons that fail to reach the opposite hemisphere, the higher number of axons present in the AC of acallosal mice may contribute to the functional compensation for the loss of the CC.

These results are not totally conclusive because the strains in question also show a number of behavioral peculiarities that are unrelated to the effects of an absent CC [2,18,20,26], and it remains possible that effects of absent CC may depend on the strain background, just as CC absence does [22]. The present paper addresses this limitation by utilizing several recombinant inbred lines created from the 129 and BALB/c strains, so that genes responsible for absence of the CC would not likely be spuriously correlated with genes relevant for abnormal behavior.The literature on humans lacking the CC points to mild, language-related deficits in intelligence and rhyming [10,24], and it suggests that deficits are most likely to appear on motor tasks, in which pressure exists to perform at high speed [14,23]. In this paper, we report that CC-related deficits in high-speed wheel running indeed appear when the task is rendered more difficult by removing several rungs from the wheel.The interpretation of behavioral test results from acallosal mice is challenging because usually no compelling reason exists to believe that the behaviors in question rely heavily on interhemispheric communication. It is also possible that as with human CC agenesis [9,11,19,29], developmental plasticity creates or pre-serves alternative

A three locus model of the inheritance of absent corpus callosum in mice was tested by creating F1 and F2 hybrid crosses from the strains BALB/cWah1 and 129/J which show incomplete penetrance for callosal agenesis. The model predicted that a few of the F2 hybrid mice would suffer severe reduction of the hippocampal commissure when the corpus callosum was absent, a condition that usually occurs only in the most consistently acallosal I/LnJ strain, and this prediction was confirmed. The C129F2 hybrid population expresses substantial genetic variation and an extremely wide range of defects of the corpus callosum, dorsal commissure of the fornix and hippocampal commissure. At the same time, these hybrids have exceptionally good health and reproductive performance, unlike their inbred parent strains. These characteristics make them ideal subjects for the study of brain-behaviour correlation using a noninvasive method.

The corpus callosum (CC) of mice was completely transsected with a thin tungsten knife using a three-cut approach through the dorsal cerebrum just lateral to midline. This method results in almost total transsection of the CC throughout its entire rostrocaudal extent. Advantages of this approach include minimal bleeding and extracallosal damage as well as the possibility of selective transsection of only anterior, middle, or posterior parts of the CC. The technique can be readily adapted to any other rodent species.