Bergson C, Mrzljak L, Smiley J F, Pappy M, Levenson R, Goldman-Rakic P S
Department of Pharmacology, Pennsylvania State College of Medicine, USA.
J Neurosci. 1995 Dec;15(12):7821-36. doi: 10.1523/JNEUROSCI.15-12-07821.1995.
The pathways governing signal transduction in the mesocortical and nigrostriatal dopamine systems of the brain are of central importance in a variety of drug actions and neurological diseases. We have analyzed the regional, cellular, and subcellular distribution of the closely related D1 and D5 subtypes of dopamine receptors in the cerebral cortex and selected subcortical structures of rhesus monkey using subtype specific antibodies. The distribution of D1 and D5 receptors was highly differentiated in subcortical structures. In the neostriatum, both D1 and to a lesser extent D5 antibodies labeled medium spiny neurons, while only D5 antibodies labeled the large aspiny neurons typical of cholinergic interneurons. In the caudate nucleus, D1 labeling was concentrated in the spines and shafts of projection neurons, whereas D5 antibodies predominantly labeled the shafts, and less commonly, the spines of these cells. The D1 receptor was abundantly expressed in the neuropil of the substantia nigra pars reticulata while the D5 antibodies labeled only a few scattered cell bodies in this structure. Conversely, D5 antibodies labeled cholinergic neurons in the basal forebrain more intensely than D1 antibodies. Within the cerebral cortex and hippocampus, D1 and D5 antibody labeling was prominent in pyramidal cells. Double-label experiments revealed that the two receptors were frequently coexpressed in neurons of both structures. Ultrastructurally, D1 receptors were especially prominent in dendritic spines whereas dendritic shafts were more prominently labeled by the D5 receptor. The anatomical segregation of the D1 and D5 receptors at the subcellular level in cerebral cortex and at the cellular level in subcortical areas suggest that these closely related receptors may be preferentially associated with different circuit elements and may play distinct regulatory roles in synaptic transmission.
大脑中脑皮质和黑质纹状体多巴胺系统中控制信号转导的通路在多种药物作用和神经疾病中至关重要。我们使用亚型特异性抗体分析了恒河猴大脑皮层和选定的皮层下结构中密切相关的多巴胺D1和D5受体亚型的区域、细胞和亚细胞分布。D1和D5受体在皮层下结构中的分布高度分化。在新纹状体中，D1和程度较轻的D5抗体标记中型多棘神经元，而只有D5抗体标记胆碱能中间神经元特有的大型无棘神经元。在尾状核中，D1标记集中在投射神经元的棘和轴突上，而D5抗体主要标记这些细胞的轴突，较少标记其棘。D1受体在黑质网状部的神经毡中大量表达，而D5抗体仅标记该结构中少数散在的细胞体。相反，D5抗体比D1抗体更强烈地标记基底前脑的胆碱能神经元。在大脑皮层和海马体内，D1和D5抗体标记在锥体细胞中很突出。双标记实验表明，这两种受体经常在这两个结构的神经元中共表达。超微结构上，D1受体在树突棘中特别突出，而D5受体在树突轴上标记更明显。大脑皮层亚细胞水平和皮层下区域细胞水平上D1和D5受体的解剖学分离表明，这些密切相关的受体可能优先与不同的神经回路元件相关联，并可能在突触传递中发挥不同的调节作用。
