Moukhles H, Amalric M, Nieoullon A, Daszuta A
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, Marseille, France.
Neuroscience. 1994 Nov;63(1):73-84. doi: 10.1016/0306-4522(94)90008-6.
The functional effects of grafts of dopamine-rich ventral mesencephalic suspension transplanted in a partially dopamine-depleted striatum were studied in rats performing a reaction-time motor task. The animals were trained to depress a lever, hold it down and release it within a limited period of time (700 ms) after the onset of a visual conditioned stimulus to obtain a food reward. The animals' performances were tested daily for up to two months after transplantation and for up to three months in the case of the animals with lesion only (bilateral striatal 6-hydroxydopamine injection). The baseline performances of the sham-operated control animals tended to improve, whereas the performances of the lesioned rats were significantly disrupted throughout the three months test. The majority of the animals (13/21) in the lesion group showed severe deficits mainly reflected in an increase in the number of the anticipated responses (premature release of the lever before the visual stimulus), and also in the number of the delayed responses (lever release after the time limit) recorded after dopamine depletion. The remaining animals (8/21) exhibited mild deficits (delayed responses only). These differences in the performance deficits appeared to be in relation to the extent of the dopamine denervation within the striatum assessed by the tyrosine hydroxylase immunostaining. Grafted animals showed a large number of dopamine fibers in the reinnervated striata and most of them (73%) significantly improved the reaction-time performance after transplantation. In the most severely impaired animals the number of anticipated errors was totally reversed within one month post-grafting, while the number of delayed responses remained high after transplantation. The performances of the less severely impaired animals returned more rapidly (within three weeks) to the pre-operative levels. The results show that intrastriatal ventral mesencephalic transplants are able to induce substantial or complete recovery in a complex reaction-time task. In the present model for partial dopamine depletion of the striatum, the mechanisms underlying the graft-induced recovery probably involve the participation of endogenous dopamine neurons acting in addition to, and/or in synergy with the dopamine-rich grafted tissue so that a functional level of dopaminergic transmission is restored in transplanted animals.
在执行反应时运动任务的大鼠中，研究了将富含多巴胺的腹侧中脑悬浮液移植到部分多巴胺耗竭的纹状体中的功能效应。训练动物在视觉条件刺激开始后的有限时间内（700毫秒）按下杠杆、按住并释放杠杆，以获得食物奖励。移植后每天对动物的表现进行测试，持续两个月，仅接受损伤的动物（双侧纹状体注射6-羟基多巴胺）则测试三个月。假手术对照动物的基线表现趋于改善，而损伤大鼠的表现在整个三个月的测试中均受到显著干扰。损伤组中的大多数动物（13/21）表现出严重缺陷，主要表现为预期反应数量增加（在视觉刺激之前过早释放杠杆），以及多巴胺耗竭后记录的延迟反应数量增加（在时间限制之后释放杠杆）。其余动物（8/21）表现出轻度缺陷（仅延迟反应）。这些表现缺陷的差异似乎与通过酪氨酸羟化酶免疫染色评估的纹状体内多巴胺去神经支配的程度有关。移植动物在重新支配的纹状体中有大量多巴胺纤维，其中大多数（73%）在移植后显著改善了反应时表现。在受损最严重的动物中，移植后一个月内预期错误的数量完全逆转，而延迟反应的数量在移植后仍然很高。受损较轻的动物的表现恢复得更快（三周内）到术前水平。结果表明，纹状体内腹侧中脑移植能够在复杂的反应时任务中诱导实质性或完全恢复。在目前部分纹状体多巴胺耗竭的模型中，移植诱导恢复的潜在机制可能涉及内源性多巴胺神经元的参与，它们与富含多巴胺的移植组织协同作用，从而在移植动物中恢复多巴胺能传递的功能水平。
