Maier D L, Kalb R G, Stelzner D J
Department of Anatomy and Cell Biology, SUNY Health Science Center, Syracuse 13210, USA.
Brain Res Dev Brain Res. 1995 Jul 14;87(2):135-44. doi: 10.1016/0165-3806(95)00065-l.
Hindlimb weight support and bipedal stepping occur after spinal cord transection in neonatal rats (birth to 12 days of age) while the same lesion in 15-day and older animals results in permanent loss of these responses. Some compensatory change in lumbar spinal circuitry must occur after spinal transection in young animals subserving these hindlimb behaviors. In contrast, animals just a few days older are incapable of such compensatory responses. We have examined the hypothesis that neural activity leads to the postnatal loss of plasticity in spinal circuitry. We find that antagonism of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor with MK-801 in young animals extends the sparing of hindlimb function after spinal transection to older animals. This effect is not due to a non-specific depression of all exciatory drive to motor neurons since Ia to motor neurons synaptic transmission through non-NMDA receptors is preserved during MK-801 treatment. Acute administration of MK-801 at the time of spinal transection or chronic administration of MK-801 after postnatal day 17 has no effect on recovery of hindlimb function after spinal transection. These results highlight the importance of NMDA receptor activation in spinal circuit maturation.
新生大鼠（出生至12日龄）脊髓横断后会出现后肢负重支撑和双足行走，而在15日龄及以上的动物中，同样的损伤会导致这些反应永久丧失。在支持这些后肢行为的幼龄动物脊髓横断后，腰段脊髓回路必定会发生一些代偿性变化。相比之下，仅几天大一点的动物则无法产生这种代偿反应。我们检验了神经活动导致脊髓回路出生后可塑性丧失的假说。我们发现，在幼龄动物中用MK-801拮抗谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型，可将脊髓横断后后肢功能的保留延长至年龄更大的动物。这种效应并非由于对运动神经元所有兴奋性驱动的非特异性抑制，因为在MK-801治疗期间，通过非NMDA受体的Ia至运动神经元的突触传递得以保留。在脊髓横断时急性给予MK-801或在出生后第17天之后慢性给予MK-801，对脊髓横断后后肢功能的恢复均无影响。这些结果突出了NMDA受体激活在脊髓回路成熟中的重要性。
