Fisher L J, Young S J, Tepper J M, Groves P M, Gage F H
Department of Neurosciences, University of California, San Diego, La Jolla 92093.
Neuroscience. 1991;40(1):109-22. doi: 10.1016/0306-4522(91)90178-q.
Both spontaneous and evoked extracellular electrophysiological activity of neurons within fetal mesencephalon suspension grafts to the dopamine-depleted striatum of rats were examined. In some cases, extracellular recording was combined with intracellular labeling to identify recorded neurons. Grafted rats displaying a complete cessation of ipsilateral rotations following amphetamine administration were examined at post-implantation time intervals of two, four, five, eight and nine months. Four separate classes of neurons were distinguished within the transplanted striatum based on electrophysiological properties. The first of these groups, the type I cells, appeared to be non-grafted striatal neurons. When spontaneously active, these striatal-like cells fired bursts of action potentials separated by periods of decreased activity. Evoked responses in these cells were characteristic of striatal cells. Type I cells which were intracellularly labeled were found outside the grafts and displayed the characteristic morphology of the medium spiny neuron of the neostriatum. The other three cell classes displayed electrophysiological properties similar to neurons recorded in situ within the reticular formation, substantia nigra pars compacta and substantia nigra pars reticulata. Neurons from these three groups which were labeled with an intracellular marker were found to lie within the suspension grafts. The spontaneous activity of the pars compacta dopaminergic-like neurons was predominantly irregular, with some cells also firing in a regular or pacemaker-like pattern. Infrequently, irregular firing dopaminergic-like neurons displayed episodes of doublet bursting. Many of the grafted neurons responded to electrical stimulation of prefrontal cortex and striatum, indicating that the graft was receiving functional inputs from host neurons. Comparison of the firing rate and pattern of grafted neurons to in situ mesencephalic neurons as a function of time following grafting suggested that the grafted neurons and/or the neuronal circuitry is slowly developing within the host environment. A prolonged time-course for the maturation of the graft may be reflected in the time required to achieve improvements in some behavioral deficits following transplantation. However, the relatively rapid recovery of drug-induced rotational asymmetry following grafting suggests that this form of recovery may not require mature functioning of the grafted neurons.
对移植到多巴胺耗竭大鼠纹状体的胎儿中脑悬浮移植物内神经元的自发和诱发细胞外电生理活动进行了检查。在某些情况下,将细胞外记录与细胞内标记相结合以识别记录的神经元。在安非他明给药后同侧旋转完全停止的移植大鼠在植入后2、4、5、8和9个月的时间间隔进行检查。根据电生理特性,在移植的纹状体内区分出四类不同的神经元。这些组中的第一类,即I型细胞,似乎是未移植的纹状体神经元。当自发活动时,这些纹状体样细胞会发放动作电位爆发,期间活动减少。这些细胞中的诱发反应是纹状体细胞的特征。细胞内标记的I型细胞在移植物外被发现,并表现出新纹状体中等棘状神经元的特征形态。其他三类细胞表现出与在网状结构、黑质致密部和黑质网状部原位记录的神经元相似的电生理特性。用细胞内标记物标记的这三组神经元位于悬浮移植物内。致密部多巴胺能样神经元的自发活动主要是不规则的,一些细胞也以规则或起搏器样模式放电。偶尔,不规则放电的多巴胺能样神经元会出现双峰爆发。许多移植神经元对前额叶皮质和纹状体的电刺激有反应,表明移植物接受来自宿主神经元的功能性输入。将移植神经元的放电率和模式与移植后不同时间的原位中脑神经元进行比较表明,移植神经元和/或神经回路在宿主环境中正在缓慢发育。移植物成熟的延长时间进程可能反映在移植后某些行为缺陷改善所需的时间上。然而,移植后药物诱导的旋转不对称相对较快的恢复表明,这种恢复形式可能不需要移植神经元的成熟功能。