Joyce J N, Marshall J F
Neuroscience. 1987 Mar;20(3):773-95. doi: 10.1016/0306-4522(87)90240-5.
Dopamine D2 receptors, labeled with [3H]spiroperidol or [3H]sulpiride, show a lateral-to-medial gradient in the caudate-putamen, with a more than two-fold greater density laterally than medially. It has been thought that D2 receptors are located on at least two neuronal elements of the caudate-putamen, neurons intrinsic to this structure and axons whose cell bodies reside in the cortex. As a first step in establishing what neuronal elements underlie this heterogeneous organization of D2 receptors, we took advantage of quantitative autoradiography to examine the association of these receptors with those elements. The present findings show that the D2 sites are almost exclusively located on neurons whose somata reside in the caudate-putamen and are not located on terminals of corticostriatal axons. A detailed comparison of the distribution of histochemically identified acetylcholinesterase neurons with that of D2 receptors in serially adjoining sections suggests a common organizational pattern. The density of [3H]spiroperidol sites in rat caudate-putamen was determined after unilateral injection of the neurotoxin quinolinic acid into this structure or after ablation of neocortical regions. Quantification of the tissue damage was achieved by acetylcholinesterase histochemistry (following diisopropylfluorophosphate treatment), as well as by thionin and luxol fast staining of sections adjacent to those used for [3H]spiroperidol autoradiography. In identically treated animals, biochemical determination of the extent of tissue damage was made utilizing assays for high-affinity [3H]choline and [3H]glutamate uptake in the caudate-putamen. In quinolinic acid-injected rats, the density of D2 sites was decreased by 90-95% at the site of complete loss of large acetylcholinesterase-positive neurons. Other animals, given ablations of specific neocortical fields (medial prefrontal, motor, somatosensory) or of the entire parietal-frontal cortex of one hemisphere, showed no loss of caudate-putamen D2 sites unless the cortical ablation caused accompanying damage of the caudate-putamen. In the caudate-putamen of all animals there was a close correspondence between the D2 sites and the striatal neurons (and processes) that show strong acetylcholinesterase reactivity. We suggest that the caudate-putamen topography of D2 sites is based largely on the internal organization of this structure and may preferentially involve acetylcholine-containing intrinsic neurons.
用[3H]螺哌啶醇或[3H]舒必利标记的多巴胺D2受体在尾状核-壳核中呈现从外侧到内侧的梯度分布，外侧密度比内侧高两倍多。人们一直认为D2受体至少位于尾状核-壳核的两种神经元成分上，即该结构固有的神经元以及胞体位于皮质的轴突。作为确定何种神经元成分构成D2受体这种异质性组织基础的第一步，我们利用定量放射自显影技术来研究这些受体与那些成分的关联。目前的研究结果表明，D2位点几乎完全位于胞体位于尾状核-壳核的神经元上，而不在皮质纹状体轴突的终末上。在连续相邻切片中，对组织化学鉴定的乙酰胆碱酯酶神经元分布与D2受体分布进行详细比较，结果显示出一种共同的组织模式。在向大鼠尾状核-壳核单侧注射神经毒素喹啉酸或切除新皮质区域后，测定了[3H]螺哌啶醇位点在大鼠尾状核-壳核中的密度。通过乙酰胆碱酯酶组织化学（在二异丙基氟磷酸处理后）以及对与用于[3H]螺哌啶醇放射自显影的切片相邻的切片进行硫堇和变色酸2R快速染色，实现了对组织损伤的定量。在相同处理的动物中，利用尾状核-壳核中高亲和力[3H]胆碱和[3H]谷氨酸摄取的测定方法，对组织损伤程度进行了生化测定。在注射喹啉酸的大鼠中，在大型乙酰胆碱酯酶阳性神经元完全丧失的部位，D2位点的密度降低了90 - 95%。其他动物，在切除特定的新皮质区域（内侧前额叶、运动、躯体感觉）或一个半球的整个顶叶-额叶皮质后，除非皮质切除导致尾状核-壳核伴随损伤，否则尾状核-壳核的D2位点没有丢失。在所有动物的尾状核-壳核中，D2位点与显示强烈乙酰胆碱酯酶反应性的纹状体神经元（及其突起）之间存在密切对应关系。我们认为，D2位点在尾状核-壳核中的拓扑结构很大程度上基于该结构的内部组织，并且可能优先涉及含乙酰胆碱的固有神经元。
