Age-dependent specification of the corticocortical connections of cerebral grafts

To investigate further the factors involved in the development of cerebral cortical circuitry, we examined the organization of corticocortical connections of heterotopic grafts of fetal cortex placed into neonatal rat cortices. Presumptive perirhinal or sensorimotor areas of the cerebral wall were removed as slabs from embryonic day 12 (E12), E13, or E14 rats and transplanted heterotopically into either rostral perirhinal or sensorimotor cortical areas of neonatal rats. Two weeks later, the afferent cortical connections of the grafts were labeled by placing DilC18(-3) (Dil) into each transplant site. Both the E12 and E13 heterotopic transplants of presumptive perirhinal cortex contain mostly precursor cells. When these grafts are placed into sensorimotor cortex, callosal connections are formed primarily with the contralateral sensorimotor (Sml) area, the normal projection of Sml cortex. In contrast, the E14 heterotopic transplants of the perirhinal cortical wall, containing many more postmitotic neurons, developed contralateral connections with both sensorimotor and rostral perirhinal cortices. Thus, when precursor cells are transplanted heterotopically, by using E12/E13 donor tissue, the grafts receive projections that are similar to those of the host cortical area. When older cortical neurons, together with precursors, are transplanted into a heterotopic cortical area, by using E14 donor tissue, their cortical connections exhibit both host and original donor phenotypes. The data are consistent with our previous analysis of thalamocortical connections of grafts (Barbe and Levitt, 1992b) and suggest the existence of a cell-cell recognition system for thalamocortical and corticocortical circuit formation, whose mechanisms of action may be linked to the timing of neurogenesis.