Cross-modal reorganization of callosal connectivity without altering thalamocortical projections

Abstract

Mammalian cerebral cortex is composed of a multitude of different areas that are each specialized for a unique purpose. It is unclear whether the activity pattern and modality of sensory inputs to cortex play an important role in the development of cortical regionalization. The modality of sensory inputs to cerebral cortex can be altered experimentally. Neonatal diversion of retinal axons to the auditory thalamus (cross-modal rewiring) results in a primary auditory cortex (AI) that resembles the primary visual cortex in its visual response properties and topography. Functional reorganization could occur because the visual inputs use existing circuitry in AI, or because the early visual inputs promote changes in AI's circuitry that make it capable of constructing visual receptive field properties. The present study begins to distinguish between these possibilities by exploring whether the callosal connectivity of AI is altered by early visual experience. Here we show that early visual inputs to auditory thalamus can reorganize callosal connections in auditory cortex, causing both a reduction in their extent and a reorganization of the pattern. This result is distinctly different from that in deafened animals, which have widespread callosal connections, as in early postnatal development. Thus, profound changes in cortical circuitry can result simply from a change in the modality of afferent input. Similar changes may underlie cortical compensatory processes in deaf and blind humans.

Figure 1

Photomicrograph of a Nissl-stained, flattened section through AI in a cross-modal ferret (the same animal as Fig. 3C). Most of this tangential 50-μm section cuts through layer 2/3, although layer 4 can be seen in the center. pes and aes, posterior and anterior ectosylvian sulci. Despite some changes in the sulcal pattern resulting from the visual cortical lesion, the cytoarchitecture looks undisturbed. (Scale bar = 2.0 mm.)

Figure 2

Pattern of callosal connections in the right AI of four normal animals after multiple injections of retro- and anterograde tracer in the contralateral AI. The ectosylvian sulcus is outlined in white in this and the other micrographs. A, B, and D are slightly more superficial sections than C, illustrating that the labeled somata in layer 2/3, which are at a deeper level than the terminals, were somewhat less restricted in their distribution than the anterogradely labeled terminals. Asterisks show the location of the two clearest stripes or bands of callosal label observed in normal animals. (Scale bar = 2.5 mm.)

Figure 3

Pattern of callosal connections in the left AI from cross-modal animals with large rerouting lesions. The panels are arranged from the smallest (IA) to the largest (D) lesion in this large lesion size class. Note that the orientation of the left AI in the micrographs of cross-modal ferret cortices (Figs. 3 and 4) has been photographically reversed from left to right to facilitate comparisons with deaf and normal animals. Tracer was injected throughout the right AI, and it revealed an absence of bands and a concentration of the label in the ventral part of the left AI. The extent of labeling was markedly reduced compared with normal animals, especially in D. (Scale bar = 2.5 mm.)

Figure 4

Pattern of callosal connections in the left AI from cross-modal animals with smaller rerouting lesions. The panels are arranged from largest (A) to smallest (D) lesion in this medium-sized lesion class, in the opposite order from Fig. 3. Tracer was injected in the right AI. A and B are from animals with larger lesions than C and D. The alterations in the callosal patterns were less severe with smaller lesions. (Scale bar = 2.5 mm.)

Figure 5

Pattern of callosal connections in early-deafened animals. The somata and terminals were more widespread than in normal or cross-modal animals. In the AI shown in A, some evidence of a banded distribution of terminals was evident, and in all of the animals there were a few patches of terminal label at the edge of the sulcus, but these were less common than in the other groups. (Scale bar = 2.5 mm.)

Figure 6

Quantitative analysis of the data. (A) Comparison of the number of patches of callosal terminal label on the ectosylvian gyrus in the three different groups. The deaf animals had significantly fewer patches. (B) Proportion of AI occupied by patches of callosal terminal label (coverage area). The patches occupied the smallest proportion of AI in the cross-modal animals. (C) Comparison of the size of patches of callosal label in AI and AII considered together. Mean patch size (area) is plotted for each group. Cross-modal animals had significantly smaller patches than the other two groups. (D) Comparison of the patches located within the estimated borders of AI for each group. Again the patches were smallest in the cross-modal animals. (E) Comparison of the shape of patches of callosal label, with respect to elongation along the major axis. A mean ratio of major to minor axis length was calculated in each case for all patches within the ectosylvian gyrus. There was a significant difference in patch elongation only between the normal and cross-modal groups. (F) Comparison of the shape of the three largest patches of callosal label revealed significant differences with respect to all comparisons.