5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex:: Possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites
5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex:: Possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites
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DOI：
10.1073/pnas.95.2.735
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发表时间：
1998-01-20
影响因子：
11.1
通讯作者：
Goldman-Rakic, PS
中科院分区：
文献类型：
--
作者：
Jakab, RL;Goldman-Rakic, PS
为了确定 5-羟色胺 (2A) (5-HT2A) 血清素受体对致幻剂和非典型抗精神病药物的作用作出反应的皮质位点，我们通过使用光学和电子显微镜检查了猕猴大脑皮层（重点是前额叶区域）中这些受体的细胞和亚细胞分布。 免疫细胞化学技术，在所有皮质层中均检测到 5-HT2A 受体免疫反应性，其中 II 层和 III 层以及 V 层和 VI 层染色强烈，IV 层标记较弱，大多数受体标记细胞是锥体神经元，最强烈的免疫标记始终局限于平行排列的近端神经元。 顶端树突在 IV 层上方和下方形成两个强烈染色的带，在双标记实验中，在钙结合蛋白 D28k 阳性、非磷酸化神经丝阳性和免疫阴性锥体细胞中发现 5-HT2A 标记，表明可能所有锥体细胞都表达 5-HT2A 受体，在大和中也发现 5-HT2A 标记。 中等大小的中间神经元，其中一些对钙结合蛋白呈免疫阳性，5-HT2A 受体标记也与轴突末端相关。这些发现通过以下方式协调了受体皮质生理学和定位的数据：(i) 确定 5-HT2A 受体位于突触后和突触前，(ii) 证明锥体神经元构成皮质中主要的 5-HT2A 受体表达细胞，以及 (iii) 支持锥体细胞近端的顶端树突区域的观点 体细胞是 5-HT2A 受体介导的生理作用的“热点”，与大脑皮层的正常和“精神病”功能状态相关。
To identify the cortical sites where 5-hydroxytryptamine(2A) (5-HT2A) serotonin receptors respond to the action of hallucinogens and atypical antipsychotic drugs, we have examined the cellular and subcellular distribution of these receptors in the cerebral cortex of macaque monkeys (with a focus on prefrontal areas) by using light and electron microscopic immunocytochemical techniques, 5-HT2A receptor immunoreactivity was detected in all cortical layers, among which layers II and III and layers V and VI were intensely stained, and layer IV was weakly labeled, The majority of the receptor-labeled cells were pyramidal neurons and the most intense immunolabeling was consistently confined to their parallelly aligned proximal apical dendrites that formed two intensely stained bands above and below layer IV, In double-label experiments, 5-HT2A label was found in calbindin D28k-positive, nonphosphorylated-neurofilament-positive, and immune-negative pyramidal cells, suggesting that probably all pyramidal cells express 5-HT2A receptors, 5-HT2A label was also found in large-and medium-size interneurons, some of which were immune-positive for calbindin, 5-HT2A receptor label was also associated with axon terminals. These findings reconcile the data on the receptor's cortical physiology and localization by (i) establishing that 5-HT2A receptors are located postsynaptically and presynaptically, (ii) demonstrating that pyramidal neurons constitute the major 5-HT2A-receptor-expressing Cells in the cortex, and (iii) supporting the view that the apical dendritic field proximal to the pyramidal cell soma is the "hot spot" for 5-HT2A-receptor-mediated physiological actions relevant to normal and "psychotic" functional states of the cerebral cortex.