Vickers J C, Huntley G W, Edwards A M, Moran T, Rogers S W, Heinemann S F, Morrison J H
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029.
J Neurosci. 1993 Jul;13(7):2982-92. doi: 10.1523/JNEUROSCI.13-07-02982.1993.
Excitatory amino acid transmission has been proposed as the principal synaptic mechanism for distribution of information through corticocortical and thalamocortical pathways. The following study utilized a double labeling paradigm, using antibodies that recognize non-NMDA ionotropic glutamate receptor subunits and other neuronal markers, to further define, quantitatively, the subclasses of neurons that contain immunoreactivity for the AMPA/kainate and kainate receptor subunits in the monkey prefrontal cortex. Double labeling with an antibody that recognizes common epitopes in AMPA/kainate subunits GluR2 and GluR3 (GluR2/3) in combination with an antibody that recognizes the kainate receptor subunits GluR5, GluR6, and GluR7 (GluR5/6/7) demonstrated that immunoreactivity for these two receptor classes was highly colocalized in a great majority of the pyramidal neurons in this region but present in only a minority of neurochemically identified subclasses of GABAergic interneurons. Furthermore, GluR2/3 immunoreactivity had principally a somatic distribution whereas GluR5/6/7 labeling was predominately found in the perikarya and/or particular dendritic domains. In contrast, intense GluR1 labeling was observed in a small subpopulation of interneurons and low GluR1 immunoreactivity was present in many other cortical neurons. These results demonstrate that there is a high degree of specificity in the distribution of AMPA/kainate and kainate receptor-class proteins to subclasses of neurons within the neocortex. A neuron's combination of excitatory amino acid receptor subunits may regulate its response to excitatory inputs and further defines the role of identified subclasses of neurons in the complex circuitry of the cerebral cortex and may also indicate the basis for the apparent cellular selectivity of excitotoxic degenerative processes.
兴奋性氨基酸传递被认为是通过皮质-皮质和丘脑-皮质通路进行信息分布的主要突触机制。以下研究采用双标记范式,使用识别非NMDA离子型谷氨酸受体亚基和其他神经元标志物的抗体,以进一步定量地确定在猴前额叶皮质中对AMPA/海人藻酸受体亚基和海人藻酸受体亚基具有免疫反应性的神经元亚类。用识别AMPA/海人藻酸亚基GluR2和GluR3(GluR2/3)中共同表位的抗体与识别海人藻酸受体亚基GluR5、GluR6和GluR7(GluR5/6/7)的抗体进行双标记,结果表明,这两类受体的免疫反应性在该区域的绝大多数锥体神经元中高度共定位,但仅存在于少数经神经化学鉴定的GABA能中间神经元亚类中。此外,GluR2/3免疫反应性主要分布在胞体,而GluR5/6/7标记主要见于核周体和/或特定的树突区域。相反,在一小部分中间神经元中观察到强烈的GluR1标记,而在许多其他皮质神经元中存在低水平的GluR1免疫反应性。这些结果表明,AMPA/海人藻酸和海人藻酸受体类蛋白在新皮质神经元亚类中的分布具有高度特异性。神经元兴奋性氨基酸受体亚基的组合可能调节其对兴奋性输入的反应,并进一步确定已识别的神经元亚类在大脑皮质复杂回路中的作用,还可能表明兴奋性毒性退行性过程明显的细胞选择性的基础。