Development of callosal topography in visual cortex of normal and enucleated rats

Abstract

In normal rats callosal projections in striate cortex connect retinotopically corresponding, nonmirror-symmetric cortical loci, whereas in rats bilaterally enucleated at birth, callosal fibers connect topographically mismatched, mirror-symmetric loci. Moreover, retina input specifies the topography of callosal projections by postnatal day (P)6. To investigate whether retinal input guides development of callosal maps by promoting either the corrective pruning of exuberant axon branches or the specific ingrowth and elaboration of axon branches at topographically correct places, we studied the topography of emerging callosal connections at and immediately after P6. After restricted intracortical injections of anterogradely and retrogradely transported tracers we observed that the normal, nonmirror-symmetric callosal map, as well as the anomalous, mirror-symmetric map observed in neonatally enucleated animals, are present by P6-7, just as collateral branches of simple architecture emerge from their parental axons and grow into superficial cortical layers. Our results therefore do not support the idea that retinal input guides callosal map formation by primarily promoting the large-scale elimination of long, nontopographic branches and arbors. Instead, they suggest that retinal input specifies the sites on the parental axons from which interstitial branches will grow to invade middle and upper cortical layers, thereby ensuring that the location of invading interstitial branches is accurately related to the topographical location of the soma that gives rise to the parental axon. Moreover, our results from enucleated rats suggest that the cues that determine the mirror-symmetric callosal map exert only a weak control on the topography of fiber ingrowth.

Topography and axon arbor architecture in the visual callosal pathway: effects of deafferentation and blockade of TV-methyl-D-aspartate receptors

“…The asterisk indicates that total arbor length in MK-801 treated rats (427.6 ± 43.5 μm) was significantly larger (p < 0.05) than in control rats (271.8 ± 27.8 μm). Means and STDV are graphed in B and C. Ding and Elberger, 2001;Olavarría and Safaeian, 2006). The right panel in Figure 4A illustrates our finding that neonatal enucleation increases the size of callosal arbors, and that this effect is present at early stages of development.…”

“…Our findings further suggest that NMDAR-mediated processes shape arbor architecture primarily by regulating the initial elaboration of arbors in the neocortex rather than by promoting a later-occurring pruning process. A previous study showed that callosal topography is present by P6, just as axonal branches of simple architecture grow into superficial cortical layers (Olavarría and Safaeian, 2006). If arbors develop in an exuberant fashion, this initial topography could be blurred or abolished altogether at later stages of development.…”

“…Alternatively, enucleation at birth may interfere with arbor development because of its effects on the duration of NMDARmediated responses. By P6, when invasion of supragranular layers and elaboration of arbors begin (Fish et al, 1991, Norris andKalil, 1992;Hedin-Pereira et al, 1999;Ding and Elberger, 2001;Olavarría and Safaeian, 2006), the eyes induce a lengthening of the synaptic response mediated by NMDARs in callosal cells (Olavarría et al, 2007). However, bilateral enucleation at or before P4, but not at or after P6, abolishes this transient increase in the duration of NMDAR-mediated responses (Olavarría et al, 2007).…”

“…To examine the effect of pharmacological blockade of NMDARs on the elaboration of callosal arbors, MK-801 was administered for 5 days starting at P6, when invasion of fibers into upper layers of gray matter and elaboration of arbors are just beginning (Olavarría and Safaeian, 2006). Callosal arbors were revealed with BDA injections in adult rats.…”

“…Evidence that NMDARs regulate the development of axon terminals comes from studies reporting that either blockade or cortex-specific deletion of NMDARs leads to the development of axonal arbors that are larger than normal (e.g., Brewer and Cotman, 1989;Schmidt et al, 2000;Lee et al, 2005a,b). Invasion of superficial gray matter by visual callosal axons and elaboration of terminal arbors starts by P6 in both normally eyed and neonatally enucleated rats (Olavarría and Safaeian, 2006). We examined the effect that pharmacological blockade of NMDARs starting at P6 has on the morphology of callosal arbors examined in adult rats.…”