Distinct neuronal populations specified to form corticocortical and corticothalamic projections from layer VI of developing cerebral cortex

Layer VI of the cerebral cortex contains heterogeneous populations of pyramidal neurons whose axons project either cortically or subcortically. It has been shown that a subset of layer VI neurons expressing latexin projects ipsilaterally to other cortical areas but does not contribute to the corticothalamic projections. Taking advantage of the connectional specificity of latexin-expressing neurons, we here determine whether corticocortical and corticothalamic neurons are generated at different times, and at which stage the connectional distinction develops in corticogenesis. Our experimental findings indicate that: (1) thalamic-projecting neurons in layer VI of the rat secondary somatosensory cortex (SII) are born at embryonic day 14 or before while latexin-expressing neurons in the same layer are generated at embryonic day 15 or later; (2) axonal invasion by SII neurons into ipsilateral cortical areas and into the posterior dorsal thalamus mainly takes place early in the postnatal period; (3) latexin-expressing neurons never project toward the dorsal thalamus in normal development; (4) presumptive latexin-expressing neurons in the neonatal SII are able to grow into a cortical slice in vitro, but do not invade a thalamic slice even transiently; (5) thalamic-projecting neurons, on the other hand, fail to simultaneously establish connections with a cortical slice. Taken together, our findings suggest that the time frame in which presumptive corticocortical and corticothalamic neurons are generated differs, and that the two populations are restricted in connectional fate potential by the perinatal period prior to target innervation.