Björklund A, Stenevi U, Dunnett S B, Iversen S D
Nature. 1981 Feb 5;289(5797):497-9. doi: 10.1038/289497a0.
Functional deficits following brain lesions can be due not only to the disruption of conduction in specific input and output pathways passing through the site of injury, but also to the loss of important regulatory systems controlling the functional state of neuronal circuitries in areas distant from the lesion. For example, the behavioural disturbances that result from lesions of the nigrostriatal dopamine (DA) pathways can be reversed by administration of dopamine receptor-activating drugs, such as L-dopa or apomorphine. This suggests that the lesioned dopaminergic system, rather than conveying specific input and output signals, is normally acting on neuronal machineries whose activity levels are set by the activity at the dopaminergic synapses. Thus the neurological deficits resulting from these lesions are due to functional inactivation of otherwise intact neostriatal circuitries. Previous studies have shown that intracerebral transplants of embryonic substantia nigra can compensate for drug-induced as well as spontaneous asymmetric motor behaviour (expressed as a tendency to move in circles towards the lesioned side), whereas the sensorimotor asymmetry, which is pronounced in rats with a unilateral lesion of the nigrostriatal DA pathway, was unaffected by the transplant. We report here that restoration of striatal dopaminergic neurotransmission by nigral transplants in animals with bilateral, complete lesions of the nigral transplants in animals with bilateral, complete lesions of the nigrostriatal DA pathways can reinstate not only certain aspects of spontaneous motor behavior, but also sensorimotor orientation and sensory attention on the side of the body contralateral to the graft.
脑损伤后的功能缺陷不仅可能是由于穿过损伤部位的特定输入和输出通路的传导中断，还可能是由于控制远离损伤部位的神经元回路功能状态的重要调节系统的丧失。例如，黑质纹状体多巴胺（DA）通路损伤导致的行为障碍可以通过给予多巴胺受体激活药物（如左旋多巴或阿扑吗啡）来逆转。这表明，受损的多巴胺能系统并非传递特定的输入和输出信号，而是通常作用于其活动水平由多巴胺能突触处的活动设定的神经元机制。因此，这些损伤导致的神经功能缺陷是由于原本完整的新纹状体回路功能失活所致。先前的研究表明，胚胎黑质的脑内移植可以补偿药物诱导的以及自发的不对称运动行为（表现为向损伤侧转圈的倾向），而在黑质纹状体DA通路单侧损伤的大鼠中明显的感觉运动不对称不受移植的影响。我们在此报告，在双侧黑质纹状体DA通路完全损伤的动物中，通过黑质移植恢复纹状体多巴胺能神经传递不仅可以恢复自发运动行为的某些方面，还可以恢复移植对侧身体的感觉运动定向和感觉注意力。
