Nilsson O G, Leanza G, Rosenblad C, Björklund A
Department of Medical Cell Research, University of Lund, Sweden.
Ann N Y Acad Sci. 1993 Sep 24;695:267-73. doi: 10.1111/j.1749-6632.1993.tb23065.x.
The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release exhibited normal firing-dependent properties. By applying various behaviorally arousing stimuli that normally activate the basal forebrain projection systems, we wished to investigate the functional integration of the grafts in the host brain. In the hippocampus, sensory stimulation, immobilization stress and motor activity all resulted in increased release of graft-derived ACh amounting to 25-65% of the normal response. Variations in ACh levels during the day-night cycle was, however, not observed in the grafted rats. In the frontal cortex, immobilization enhanced the graft-derived ACh release (60% of normal response), whereas the response to sensory stimulation did not reach significance. Since the activity of the normal basal forebrain projection systems is under influence of monoaminergic brainstem afferents, we investigated the effects of systemic administration of amphetamine or apomorphine on ACh release in the hippocampus. Both drugs produced increases in graft-derived ACh release although the response was variable and less pronounced than normal. In conclusion, the graft-derived ACh release was affected by behavioral manipulations and catecholaminergic drugs that normally modify cholinergic septo-hippocampal and basalo-cortical activity. This strongly suggests a high degree of functional integration of the graft in the host brain allowing for a regulated release of transmitter that can be adjusted during ongoing behavior.
通过微透析技术，在清醒大鼠中研究了移植到海马体或新皮层的胆碱能神经元释放乙酰胆碱（ACh）的调节情况。将胎儿基底前脑组织作为细胞悬液或实体移植物植入海马体穹窿 - 海马伞损伤部位，或作为细胞悬液植入基底核兴奋性毒性损伤后的额叶皮层。移植数月后，将微透析探针植入移植物重新支配的海马体或额叶皮层区域。移植物使损伤诱导的稳态ACh释放缺陷恢复到海马体和额叶皮层的正常或高于正常水平。对氯化钾和河豚毒素的反应表明，ACh释放表现出正常的放电依赖性特性。通过施加各种通常激活基底前脑投射系统的行为性唤醒刺激，我们希望研究移植物在宿主脑中的功能整合情况。在海马体中，感觉刺激、固定应激和运动活动均导致移植物衍生的ACh释放增加，达到正常反应的25%至65%。然而，在移植大鼠中未观察到昼夜周期中ACh水平的变化。在额叶皮层中，固定增强了移植物衍生的ACh释放（达到正常反应的60%），而对感觉刺激的反应不显著。由于正常基底前脑投射系统的活动受单胺能脑干传入神经的影响，我们研究了全身给予苯丙胺或阿扑吗啡对海马体中ACh释放的影响。两种药物均使移植物衍生的ACh释放增加，尽管反应可变且不如正常明显。总之，移植物衍生的ACh释放受行为操作和儿茶酚胺能药物的影响，这些药物通常会改变胆碱能隔 - 海马和基底 - 皮层的活动。这强烈表明移植物在宿主脑中高度功能整合，允许在持续行为中调节递质释放。
