Requirement for subplate neurons in the formation of thalamocortical connections

Abstract

The neurons of layer 4 in the adult cerebral cortex receive their major ascending inputs from the thalamus. In development, however, thalamic axons arrive at the appropriate cortical area long before their target layer 4 neurons have migrated into the cortical plate. The axons accumulate and wait in the zone below the cortical plate, the subplate, for several weeks before invading the cortical plate. The subplate is a transient zone that contains the first postmitotic neurons of the telencephalon. These neurons mature well before other cortical neurons, and disappear by cell death after the thalamic axons have grown into the overlying cortical plate. The close proximity of growing thalamocortical axons and subplate neurons suggests that they might be involved in interactions important for normal thalamocortical development. Here we show that early in development the deletion of subplate neurons located beneath visual cortex prevents axons from the lateral geniculate nucleus of the thalamus from recognizing and innervating visual cortex, their normal target. In the absence of subplate neurons, lateral geniculate nucleus axons continue to grow in the white matter past visual cortex despite the presence of their target layer 4 neurons. Thus the transient subplate neurons are necessary for appropriate cortical target selection by thalamocortical axons.

Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation

“…Previous findings show that thalamic axons must interact with subplate cells to recognize target areas (Ghosh et al, 1990;Ghosh and Shatz, 1993;Allendoerfer and Shatz, 1994;O'Leary et al, 1994;Molnar et al, 1998b). When the subplate beneath primary sensory cortex was ablated in the cat, axons from sensory thalamus did not enter the cortical plate, either in the target area or in other areas with an intact subplate (Ghosh et al, 1990;Ghosh and Shatz, 1993).…”

“…Initially, thalamocortical axons are sorted in the IC by subcortical molecular guidance cues that are themselves independent of the cortex (Braisted et al, 2000;Garel et al, 2002;Hevner et al, 2002;Lopez-Bendito et al, 2002;Dufour et al, 2003;Seibt et al, 2003;Garel and Rubenstein, 2004) and from intracortical FGF8/17 signaling (present study). Once axons reach the subplate, they are guided sequentially by positional information in the subplate and the developing layers of the cortical plate (Ghosh et al, 1990(Ghosh et al, , 1993present study). Intracortical and subcortical mechanisms can function together to guide thalamocortical innervation because they are normally in spatial register.…”

LIS1—no more no less

“…It has been hypothesized that the maturation of neurons in the cortical plate plays a crucial role in the invasion of layer 4 by thalamocortical afferent axons. [65][66][67][68] The retarded development of the cortical plate in Lis1/sLis1 embryos led us to speculate that axonal development might be altered as well, and indeed the projections of thalamo-cortical axons were markedly reduced in the mutant embryos. We followed the progression of neuronal migration, and by injection of BrdU at E13.5, followed by sacrifice at E15.5, revealed differences in the pattern and distribution of labeled cells in the occipital cortex.…”

Extrapolating brain development from experimental species to humans

“…The result is a variety of data obtained in species born at a wide range of developmental stages and maturing at different rates, but with little explicit agreement or common understanding on how to relate them to humans. For example, how might we best study the effects of toxins on the crucial first-generated cortical cells (subplate cells) when initial studies describing these cells were done in macaques (Kostovic and Rakic, 1980), later studies used cats (Chun and Shatz, 1989;Ghosh et al, 1990), rats (Bayer and Altman, 1990) and hamsters (Miller et al, 1993;Woo and Finlay, 1996), and future studies are likely to be accomplished in mice?…”