TOPOGRAPHIC SPECIFICITY OF CORTICOSPINAL CONNECTIONS FORMED IN EXPLANT COCULTURE

The corticospinal pathway connects layer V pyramidal neurons in discre te regions of the sensorimotor cortex to topographically matching targ ets in the spinal cord. In rodents initial pathway errors occur transi ently during early postnatal development, such that visual cortical ax ons project inappropriately into the corticospinal tract, Nevertheless , only sensorimotor axons form corticospinal connections, which are to pographically ordered in hamsters from the earliest stages of innervat ion. Previous work in vivo suggests that pathfinding is carried out by primary cortical axons whereas target innervation occurs by extension of axon collaterals at appropriate locations. In vitro studies have p rovided evidence that chemotropic factors may selectively attract exte nsion of neurites into specific targets. To investigate the basis for corticospinal target selection during development, we have used an in vitro explant coculture system. Sensorimotor and visual cortical expla nts from newborn hamsters were presented with inappropriate targets fr om olfactory bulb and cerebellum and targets from the cervical (foreli mb) and lumbar (hindlimb) enlargements of the early postnatal spinal c ord. Under in vitro conditions, corticospinal target selection was hig hly specific and remarkably similar to corticospinal connectivity in v ivo. Visual and sensorimotor cortical neurites extended nonselectively into the white matter of the spinal cord. However, only neurites from the sensorimotor cortex were able to extend into and arborize within the spinal gray. In the majority of cases, these connections were topo graphically appropriate, matching forelimb cortex to cervical cord and hindlimb cortex to lumbar cord. However, we found no evidence that ch emotropic attraction was responsible for selection of appropriate targ ets by cortical neurites or that spinal target tissue promoted extensi on of cortical axon collaterals within the collagen matrix. These resu lts suggest that the ability of cortical neurites to recognize correct spinal targets and form terminal arbors may require direct axon targe t interaction.