DEVELOPMENT OF SPECIFICITY IN CORTICOSPINAL CONNECTIONS BY AXON COLLATERALS BRANCHING SELECTIVELY INTO APPROPRIATE SPINAL TARGETS

Corticospinal projections in adult rodents arise exclusively from laye r V neurons in the sensorimotor cortex. These neurons are topographica lly organized in their connections to spinal cord targets. Previous st udies in rodents have shown that the mature distribution pattern of co rticospinal neurons develops during the first 2 weeks postnatal from a n initial widespread pattern that includes the visual cortex to a dist ribution restricted to the sensorimotor cortex. To determine whether s pecificity in corticospinal connections also emerges from an initially diffuse set of projections, we have studied the outgrowth of corticos pinal axons and the formation of terminal arbors in developing hamster s. The sensitive fluorescent tracer 1,1',dioctadecyl-3,3,3',3'-tetrame thylindocarbocy perchlorate (DiI) was used to label corticospinal axon s from the visual cortex or from small regions of the forelimb or hind limb sensorimotor cortex in Living animals at 4-17 days postnatal. Ini tially axon outgrowth was imprecise. Some visual cortical axons extend ed transiently beyond their permanent targets in the pontine nuclei, b y growing through the pyramidal decussation and in some cases extendin g as far caudally as the lumbar enlargement. Forelimb sensorimotor axo ns also extended past their targets in the cervical enlargement, in ma ny cases growing in the corticospinal tract to lumbar levels of the co rd. By about 17 days postnatal these misdirected axons or axon segment s were withdrawn from the tract. Despite these errors in axon trajecto ries within the corticospinal tract, terminal arbors branching into ta rgets in the spinal gray matter were topographically appropriate from the earliest stages of innervation. Thus visual cortical axons never f ormed connections in the spinal cord, forelimb sensorimotor axons arbo rized only in the cervical enlargement, and hindlimb cortical axons te rminated only in the lumbar cord at all stages of development examined . Corticospinal arbors formed from collaterals that extended at right angles from the shafts of primary axons, most likely by the process of interstitial branching after the primary growth cone had extended pas t the target. Once collaterals extended into the spinal gray matter, h ighly branched terminal arbors formed within 2-4 days, beginning at ab out 4 and 8 days postnatal for the cervical and lumbar enlargements, r espectively. These results show that specificity in corticospinal conn ectivity is achieved by selective growth of axon collaterals into appr opriate spinal targets from the beginning and not by the later remodel ing of initially diffuse connections. In contrast, errors occur in the initial outgrowth of axons in the corticospinal tract, which are subs equently corrected. (C) 1994 Wiley-Liss, Inc.