The use of behavioral methods to predict spinal cord plasticity

Abstract

The mechanisms underlying recovery of function following damage to the CNS, although suspected, are virtually unknown. After damage to the adult cat spinal cord, recovery of motor behavior depends on which systems have been interrupted and which remain intact. For example, following hemisection, overground (voluntary) and reflex locomotion recover and, although a normal kinematic pattern recovers, accurate placement of the limb during locomotion does not return to normal levels. This recovery is associated with lowering of thresholds for postural reflexes suggesting that increased afferent input may compensate for diminished descending control. In contrast, after unilateral loss of afferent input by lumbosacral deafferentation, (L₁-S₂ dorsal roots cut) overground locomotion recovers but a permanently abnormal kinematic pattern is used; reflex locomotion (bipedal locomotion on a treadmill) does not recover at all in the deafferented hindlimb. The specificity of the recovery suggests that increased input from descending pathways, which is required for overground but not reflex locomotion may compensate for loss of afferent input. Anatomical sequellae of these two lesion types have been examined. Studies after hemisection support the notion of a permanently increased dorsal root input as mapped by monoclonal antibody ‘rat 102’. This is associated with a transient increase in GAP-43 labeling in the dorsal horn. In contrast, after deafferentation an increase is found in the descending serotonergic input to the deafferented side. These observations suggest that recovery of specific locomotor behavior can be used to predict compensatory changes in spared pathways. For the study of the effects of transplants, we have used complete spinal transections in newborn kittens with transplantation of E26 cat spinal cord into the transection site. The normal kitten develops overground locomotion beginning the end of the first week postnatal but reflex locomotion is delayed until the end of the second week. After transection on the first day of life, with or without a transplant, reflex locomotion begins precociously. Overground locomotion fails to develop in transection-only animals but does develop in animals with transection and transplant. This locomotion although clearly abnormal, shows postnatal development in terms of weight support and lateral stability. Furthermore, there is some indication of coordination between fore and hind limbs. These observations suggest that the transplants permit the development of some descending control although the anatomical correlates of this sparing/recovery of function are uncertain; the transplant rescues neurons caudal to the transection and also permits regeneration of some descending pathways into the transplant and caudally into host spinal cord.