Quantitative autoradiography of major neurotransmitter receptors in the monkey striate and extrastriate cortex.
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.
Rakic
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Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510.
Goldman-Rakic
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PS
Gallager
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D
D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000032:analysis*; D003000:Clonidine / Q000378:metabolism; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D007650:Ketanserin / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009118:Muscimol / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000032:analysis*; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D014793:Visual Cortex / Q000032:analysis*
D017981:Receptors, Neurotransmitter; D009118:Muscimol; D012701:Serotonin; D013134:Spiperone; D005445:Flunitrazepam; D011813:Quinuclidinyl Benzilate; C029247:3-iodopindolol; D007650:Ketanserin; D010869:Pindolol; D003000:Clonidine; D011224:Prazosin