Journal of Neuroscience, Vol 8, 3670-3690, Copyright © 1988 by Society for Neuroscience
Quantitative autoradiography of major neurotransmitter receptors in the monkey striate and extrastriate cortex
P Rakic, PS Goldman-Rakic and D Gallager
Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510.
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.