Van Luijtelaar M G, Tonnaer J A, Frankhuijzen A L, Dijkstra H, Hagan J J, Steinbusch H W
Department of Pharmacology, Free University, Amsterdam, The Netherlands.
Neuroscience. 1991;42(2):365-77. doi: 10.1016/0306-4522(91)90381-w.
A procedure was developed to conduct simultaneously immunocytochemical and neurochemical studies on the serotonergic system in adjacent 300-micron-thick slices of rat hippocampus. This procedure was applied to correlate morphological (innervation pattern and density), neurochemical (5-hydroxytryptamine and 5-hydroxyindolacetic acid levels and [3H]5-hydroxytryptamine uptake and release) and behavioral (spatial learning) effects of neurotoxin-induced denervation and reinnervation by grafting fetal mesencephalic raphe cells. Intracerebroventricular injections of a low dose of 5,7-dihydroxytryptamine caused a discrete serotonergic denervation of the hippocampus. Eleven months after lesioning, 5-hydroxytryptamine and 5-hydroxyindolacetic acid levels and [3H]5-hydroxytryptamine uptake capacity were decreased by 50-60%. By this time, the residual fibers displayed an enhanced vulnerability towards K(+)-induced depolarization. Grafting of a fetal raphe cell suspension resulted in a reinnervation of the host hippocampus. The pattern of reinnervation was comparable to control innervation and the density was supranormal at the level of the graft. As observed semiquantitatively, the innervation density decreased with distance from the core of the graft. Neurochemical studies showed that the fibers were capable of synthesizing, metabolizing and releasing 5-hydroxytryptamine. The turnover of 5-hydroxytryptamine in both the denervated and the reinnervated hippocampus was comparable to that in control tissue. Previous behavioral testing of the denervated and of the denervated and implanted animals did not reveal any effect on spatial learning, either in an individual or in a social test paradigm. The latter data substantiate the notion that interference with the hippocampal serotonergic innervation does not hamper adequate spatial learning.
已开发出一种程序，可对大鼠海马体相邻300微米厚切片中的血清素能系统同时进行免疫细胞化学和神经化学研究。该程序用于关联神经毒素诱导的去神经支配和通过移植胎儿中脑缝际细胞进行再支配的形态学（神经支配模式和密度）、神经化学（5-羟色胺和5-羟吲哚乙酸水平以及[³H]5-羟色胺摄取和释放）和行为学（空间学习）效应。脑室内注射低剂量的5,7-二羟基色胺会导致海马体出现离散性血清素能去神经支配。损伤11个月后，5-羟色胺和5-羟吲哚乙酸水平以及[³H]5-羟色胺摄取能力降低了50% - 60%。此时，残留纤维对钾离子诱导的去极化表现出增强的易损性。移植胎儿缝际细胞悬液可使宿主海马体重新获得神经支配。再支配模式与对照神经支配相当，且在移植物水平上密度超正常。半定量观察显示，神经支配密度随距移植物核心距离的增加而降低。神经化学研究表明，这些纤维能够合成、代谢和释放5-羟色胺。去神经支配和再神经支配的海马体中5-羟色胺的周转率与对照组织相当。先前对去神经支配动物以及去神经支配并植入移植物的动物进行的行为测试表明，无论是在个体测试还是社交测试范式中，对空间学习均未显示出任何影响。后一组数据证实了这样一种观点，即干扰海马体血清素能神经支配不会妨碍充分的空间学习。
