Rakic P, Goldman-Rakic P S, Gallager D
Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510.
J Neurosci. 1988 Oct;8(10):3670-90. doi: 10.1523/JNEUROSCI.08-10-03670.1988.
In vitro autoradiography was used to determine the binding properties and distribution of 9 major neurotransmitter receptors and their subtypes in the striate (area 17 of Brodmann) and extrastriate (areas 18 and 19) cortex of 1 infant and 3 adult rhesus monkeys. Differences in total labeling and nonspecific labeling, as well as Kd and Bmax values, were determined for all cortical layers and sublayers in both cytoarchitectonic areas by Scatchard analysis of autoradiograms. Area 17 differed from area 18 in the laminar pattern and density of virtually every ligand examined, i.e., 3H-clonidine, 3H-prazosin, 125I-iodopindolol, 3H-quinuclidinyl benzilate, 3H-5-hydroxytryptamine, 3H-ketanserin, 3H-muscimol, 3H-flunitrazepam, and 3H-spiperone. Kd and Bmax values for each ligand were remarkably consistent across the 3 adult monkeys analyzed quantitatively. Particularly dramatic contrasts were observed with clonidine, 5-hydroxytryptamine, and ketanserin, which have high affinity for alpha 2-adrenergic, 5-HT1-, and 5-HT2-receptors, respectively. The differences in distribution of these ligands, especially clonidine and 5-hydroxytryptamine, correlated well with specific laminae and hence exhibited distinctly different patterns in areas 17 and 18. Other ligands, such as flunitrazepam and quinuclidinyl benzilate that bind to GABAergic and cholinergic receptors, were visually less discriminating both among layers and between regions. However, layer for layer, the Bmax values for quinuclidinyl benzilate were higher in area 17 than 18, indicating the subtle differences between areas may be revealed only by quantitative measures. Some ligands were particularly dense in layer I (iodopindolol in areas 17 and 18; 5-hydroxytryptamine in area 18), and others subdivided cortical layers that are otherwise cytoarchitectonically uniform (e.g., flunitrazepam and clonidine in layer VI of area 17), indicating that areal differences in ligand binding are not a simple read-out of cell-packing density but most likely reflect a genuine difference related to the neurotransmitters of intrinsic and extrinsic afferents in each area. The presence of binding sites in every layer of both areas for all ligands examined indicates that their distribution across laminae is quantitative and not all-or-none. No layer contained less than 50% of binding sites present in any other layer. These findings reveal that visual cortical areas differ in density and lamination of neurotransmitter receptors and presumably in their sensitivity to circulating levels of endogenous neurotransmitters and pharmacologically active compounds.
采用体外放射自显影法,测定了1只幼年和3只成年恒河猴纹状皮质(布罗德曼17区)和纹外皮质(18区和19区)中9种主要神经递质受体及其亚型的结合特性和分布情况。通过对放射自显影片进行Scatchard分析,确定了两个细胞构筑区所有皮质层和亚层的总标记和非特异性标记差异,以及解离常数(Kd)和最大结合容量(Bmax)值。在几乎每一种检测的配体中,即3H-可乐定、3H-哌唑嗪、125I-碘吲哚洛尔、3H-喹核醇基苯甲酸酯、3H-5-羟色胺、3H-酮色林、3H-蝇蕈醇、3H-氟硝西泮和3H-螺哌隆,17区和18区在层状模式和密度上存在差异。在对3只成年猴子进行定量分析时,每种配体的Kd和Bmax值非常一致。尤其显著的对比出现在可乐定、5-羟色胺和酮色林上,它们分别对α2-肾上腺素能受体、5-HT1受体和5-HT2受体具有高亲和力。这些配体分布的差异,尤其是可乐定和5-羟色胺,与特定的层密切相关,因此在17区和18区呈现出明显不同的模式。其他与GABA能和胆碱能受体结合的配体,如氟硝西泮和喹核醇基苯甲酸酯,在层间和区域间的视觉区分度较低。然而,逐层面来看,喹核醇基苯甲酸酯在17区的Bmax值高于18区,这表明区域间的细微差异可能仅通过定量测量才能揭示。一些配体在I层特别密集(17区和18区的碘吲哚洛尔;18区的5-羟色胺),还有一些将原本细胞构筑均匀的皮质层进一步细分(例如17区VI层的氟硝西泮和可乐定),这表明配体结合的区域差异并非简单地反映细胞堆积密度,而很可能反映了与每个区域内源性和外源性传入神经递质相关的真正差异。在所检测的所有配体中,两个区域的每一层都存在结合位点,这表明它们在各层中的分布是定量的,并非全或无。没有一层所含的结合位点少于其他任何一层的50%。这些发现表明,视皮质区域在神经递质受体的密度和分层方面存在差异,推测它们对内源性神经递质和药理活性化合物循环水平的敏感性也存在差异。