NMDA ANTAGONISM DURING DEVELOPMENT EXTENDS SPARING OF HINDLIMB FUNCTION TO OLDER SPINALLY TRANSECTED RATS

Hindlimb weight support and bipedal stepping occur after spinal cord t ransection in neonatal rats (birth to 12 days of age) while the same l esion in 15-day and older animals results in permanent loss of these r esponses. Some compensatory change in lumbar spinal circuitry must occ ur after spinal transection in young animals subserving these hindlimb behaviors. In contrast, animals just a few days older are incapable o f such compensatory responses. We have examined the hypothesis that ne ural activity leads to the postnatal loss of plasticity in spinal circ uitry. We find that antagonism of the N-methyl-D-aspartate (NMDA) subt ype of glutamate receptor with MK-801 in young animals extends the spa ring of hindlimb function after spinal transection to older animals. T his effect is not due to a non-specific depression of all exciatory dr ive to motor neurons since Ia to motor neuron synaptic transmission th rough non-NMDA receptors is preserved during MK-801 treatment. Acute a dministration of MK-801 at the time of spinal transection or chronic a dministration of MK-801 after postnatal day 17 has no effect on recove ry of hindlimb function after spinal transection. These results highli ght the importance of NMDA receptor activation in spinal circuit matur ation.