Determinants of locomotor recovery after spinal injury in the cat.

After a spinalization at the most caudal thoracic spinal segment, the cat can recover locomotion of the hindlimbs when they are placed on a moving treadmill. This chapter summarizes some of the determinants of such a dramatic recovery of motor function. Fundamental to this recovery is undoubtedly the genetically based spinal locomotor generator, which provides an essential rhythmicity to spinal motoneurons and hence the musculature. Other factors are also important, however. Sensory feedback is essential for the correct expression of spinal locomotion because spinal cats, devoid of cutaneous feedback from the hindfeet, are incapable of plantar foot placement. The neurochemical environment also adapts to spinalization, i.e., the loss of all modulation by descending monoaminergic pathways. Post-transection spinal rhythmicity then becomes more dependent on glutamatergic mechanisms. Finally, we argue that the mid-lumbar spinal segments evolve to play a crucial role in the elaboration of spinal locomotion as their inactivation abolishes spinal locomotion. In summary, the above findings suggest that the recovery of spinal locomotion is determined by a number of factors, each of which must now be more fully understood in the ever-continuing effort to improve the rehabilitation of spinal-cord-injured subjects.

Effects of intrathecal glutamatergic drugs on locomotion. II. NMDA and AP-5 in intact and late spinal cats.

In a previous article, we have shown that, in cats, intrathecal injections of N-methyl-D-aspartate (NMDA) in the first few days after spinalization at T13 do not induce locomotion as in many other spinal preparations. This is in contrast to alpha-2 noradrenergic receptor stimulation, which can trigger locomotion at this early stage. However, it is known that spinal cats do recover spontaneous locomotion in the absence of descending noradrenergic pathways and that the spinal pattern generator must then depend on other neurotransmitters still present in the cord such as excitatory amino acids. In the present paper, therefore we look at the effects of intrathecal NMDA, a glutamatergic agonist, and 2-amino-5-phosphonovaleric acid (AP-5), an NMDA receptor blocker, in both intact and late spinal cats. Low doses of NMDA had no major effect on the locomotor pattern in both intact and late spinal cats. Larger doses of NMDA in the chronic spinal cat initially produced an increase in the general excitability followed by more regular locomotion. AP-5 in intact cats caused a decrease in the amplitude of the flexion reflex and induced a bilateral foot drag as well as some decrease in weight support but it did not prevent locomotion. However, in late spinal cats, the same dose of AP-5 blocked locomotion completely. These results indicate that NMDA receptors may be critical for the spontaneous expression of spinal locomotion. It is proposed that the basic locomotor rhythmicity in cats is NMDA-dependent and that normally this glutamatergic mechanism is modulated by other neurotransmitters, such as 5-HT and NA.