Attraction Exerted in Vivo by Grafts of Embryonic Neocortex on Developing Thalamic Axons

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In a previous study we provided evidence that embryonic (E) day 16 frontal cortical cells grafted into the occipital cortex of newborn rats receive inputs from the ventrolateral (VL) and ventromedial (VM) thalamic nuclei which, normally, project to the frontal cortex (25). The present study was designed to examine further the conditions of development of the thalamic innervation of heterotopic neocortical grafts. We demonstrate that VL/VM axons do not provide transitory aberrant input to the occipital cortex either in intact newborn animals or in rats having received neonatal occipital lesion and subsequent graft of E16 occipital cells. These findings indicate, therefore, that the VL/VM projection to the graft does not result from the stabilization of an initial widespread cortical projection from these thalamic nuclei occurring either spontaneously or in response to the lesion and homotopic transplantation procedures. We also show that the VL/VM projection to frontal-to-occipital grafts develops within a few days posttransplantation and is maintained in adulthood. Finally, this study establishes that most VL/VM axons which enter the grafts are not collaterals of thalamofrontal axons. After having reached the cortex, they proceed caudally primarily within the infragranular layers. The findings of this and previous (25) in vivo studies for the first time provide evidence that developing thalamic axons have the capacity to respond to signals from grafts of E16 cortical cells and are capable of deviating their trajectory to establish contact with the grafts. Only those axons arising from thalamic nuclei appropriate for the cortical locus of origin of the grafted cells respond to the guidance signals. The mechanisms by which the thalamic axons find their way to the graft probably rely on cell-contact signaling and/or long-range attraction exerted by diffusible molecules.