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P S Goldman-Rakic

Publications and source records attributed to P S Goldman-Rakic.

At least 145 records · Page 8Linked to original sources
PubMed1989

Regional differences in the distribution of muscarinic cholinergic receptors in the macaque cerebral cortex.

The in vitro autoradiographic technique was used to characterize the density and laminar distribution of muscarinic cholinergic receptors in 12 cytoarchitectonic areas in the frontal, parietal, and occipital lobes of the rhesus monkey. The entire population of muscarinic receptors was labeled with [3H]quinuclidinyl-benzilate; the M1 receptor subtype was labeled with [3H]pirenzepine; and the density of the M2 receptor subtype was estimated by subtracting the density of M1 receptors from the total population. The overall density of M1 and M2 receptor subtypes was similar throughout the cerebral cortex. However, their laminar distribution varied regionally. In cortical regions of the parietal and occipital lobes and in the primary motor cortex of the frontal lobe, both M1 and M2 receptor subtypes were concentrated in the supragranular layers. By contrast, in prefrontal cortical areas, the combined population of M1 and M2 receptors was evenly distributed across the cortical layers, though M1 receptors were most dense and M2 receptors least dense in layer IV. The difference in the distribution of cholinergic receptors in the prefrontal cortex compared to other neocortical areas reveals a degree of chemoarchitectural specificity of this region with respect to cholinergic markers that has escaped immunohistochemical and other anatomical and functional techniques.

Animals↗
PubMed1989

Distribution of cat-301 immunoreactivity in the frontal and parietal lobes of the macaque monkey.

The distribution of the monoclonal antibody Cat-301 was examined in the frontal and parietal cortex of macaque monkeys. In both regions the distribution was uniform within cytoarchitecturally defined areas (or subareas) but varied between them. In all areas, Cat-301 labeled the soma and proximal dendrites of a restricted population of neurons. In the frontal lobe, Cat-301-positive neurons were intensely immunoreactive and present in large numbers in the motor cortex (area 4), premotor cortex (area 6, excluding its lower ventral part), the supplementary motor area (SMA), and the caudal prefrontal cortex (areas 8a, 8b and 45). In the parietal lobe, large numbers of intensely immunoreactive neurons were evident in the post-central gyrus (areas 1 and 2), the superior parietal lobule (PE/5), and the dorsal bank (PEa), fundus (IPd), and deep half of the ventral bank (POa(i] of the intraparietal sulcus (IPS). Two major patterns of laminar distribution were evident. In motor, supplementary motor, premotor (excluding the lower part of its ventral division), and the caudal prefrontal cortex (Walker's areas 8a, 8b and 45), and throughout the parietal cortex (with the exception of area 3), Cat-301-positive neurons were concentrated in the lower part of layer III and in layer V. The laminar positions of labeled cells in these areas were remarkably constant, as were the proportions of labeled neurons that had pyramidal and nonpyramidal morphologies (means of 30.2% and 69.8%, respectively). In contrast, in prefrontal areas 9, 10, 11, 12, 13, 14, and 46, in the cingulate cortex (areas 23, 24 and 25), and in the lower part of the ventral premotor cortex, Cat-301-positive neurons were spread diffusely across layers II to VI and a mean of 3.6% of the labeled neurons were pyramidal while 96.4% were nonpyramidal. Area 3 was unique among frontal and parietal areas, in that the labeled neurons in this area were concentrated in layers IV and VI. The areas in the frontal lobe which were heavily labeled are thought to be involved in the control of somatic (areas 4 and 6) and ocular (areas 8 and 45) movements. Those in parietal cortex may be classified as areas with somatosensory functions (1, 2, PE/5, and PEa) and areas which may participate in the analysis of visual motion (Pandya and Seltzer's IPd and POa(i), which contain Maunsell and Van Essen's VIP). The parietal somatosensory areas are connected to frontal areas with somatic motor functions, while POa(i) is interconnected with the frontal eye fields (8a and 45).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Posterior parietal cortex in rhesus monkey: I. Parcellation of areas based on distinctive limbic and sensory corticocortical connections.

Injections of HRP-WGA in four cytoarchitectonic subdivisions of the posterior parietal cortex in rhesus monkeys allowed us to examine the major limbic and sensory afferent and efferent connections of each area. Area 7a (the caudal part of the posterior parietal lobe) is reciprocally interconnected with multiple visual-related areas: the superior temporal polysensory area (STP) in the upper bank of the superior temporal sulcus (STS), visual motion areas in the upper bank of STS, the dorsal prelunate gyrus, and portions of V2 and the parieto-occipital (PO) area. Area 7a is also heavily interconnected with limbic areas: the ventral posterior cingulate cortex, agranular retrosplenial cortex, caudomedial lobule, the parahippocampal gyrus, and the presubiculum. By contrast, the adjacent subdivision, area 7ip (within the posterior bank of the intraparietal sulcus), has few limbic connections but projects to and receives projections from widespread visual areas different than those that are connected with area 7a: the ventral bank and fundus of the STS including part of the STP cortex and the inferotemporal cortex (IT), areas MT (middle temporal) and possibly MTp (MT peripheral) and FST (fundal superior temporal) and portions of V2, V3v, V3d, V3A, V4, PO, and the inferior temporal (IT) convexity cortex. The connections between posterior parietal areas and visual areas located on the medial surface of the occipital and parieto-occipital cortex, containing peripheral representations of the visual field (V2, V3, PO), represent a major previously unrecognized source of visual inputs to the parietal association cortex. Area 7b (the rostral part of the posterior parietal lobe) was distinctive among parietal areas in its selective association with somatosensory-related areas: S1, S2, 5, the vestibular cortex, the insular cortex, and the supplementary somatosensory area (SSA). Like 7ip, area 7b had few limbic associations. Area 7m (on the medial posterior parietal cortex) has its own topographically distinct connections with the limbic (the posterior ventral bank of the cingulate sulcus, granular retrosplenial cortex, and presubiculum), visual (V2, PO, and the visual motion cortex in the upper bank of the STS), and somatosensory (SSA, and area 5) cortical areas. Each parietal subdivision is extensively interconnected with areas of the contralateral hemisphere, including both the homotopic cortex and widespread heterotopic areas. Indeed, each area is interconnected with as many areas of the contralateral hemisphere as it is within the ipsilateral one, though less intensively. This pattern of distribution allows for a remarkable degree of interhemispheric integration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe.

We have examined the circuitry connecting the posterior parietal cortex with the frontal lobe of rhesus monkeys. HRP-WGA and tritiated amino acids were injected into subdivisions 7m, 7a, 7b, and 7ip of the posterior parietal cortex, and anterograde and retrograde label was recorded within the frontal motor and association cortices. Our main finding is that each subdivision of parietal cortex is connected with a unique set of frontal areas. Thus, area 7m, on the medial parietal surface, is interconnected with the dorsal premotor cortex and the supplementary motor area, including the supplementary eye field. Within the prefrontal cortex, area 7m's connections are with the rostral sector of the frontal eye field (FEF), the dorsal bank of the principal sulcus, and the anterior bank of the inferior arcuate sulcus (Walker's area 45). In contrast, area 7a, on the posterior parietal convexity, is not linked with premotor regions but is heavily interconnected with the rostral FEF in the anterior bank of the superior arcuate sulcus, the dorsolateral prefrontal convexity, the rostral orbitofrontal cortex, area 45, and the fundus and adjacent cortex of the dorsal and ventral banks of the principal sulcus. Area 7b, in the anterior part of the posterior parietal lobule, is interconnected with still a different set of frontal areas, which include the ventral premotor cortex and supplementary motor area, area 45, and the external part of the ventral bank of the principal sulcus. The prominent connections of area 7ip, in the posterior bank of the intraparietal sulcus, are with the supplementary eye field and restricted portions of the ventral premotor cortex, with a wide area of the FEF that includes both its rostral and caudal sectors, and with area 45. All frontoparietal connections are reciprocal, and although they are most prominent within a hemisphere, notable interhemispheric connections are also present. These findings provide a basis for a parcellation of the classically considered association cortex of the frontal lobe, particularly the cortex of the principal sulcus, into sectors defined by their specific connections with the posterior parietal subdivisions. Moreover, the present findings, together with those of a companion study (Cavada and Goldman-Rakic: J. Comp. Neurol. this issue) have allowed us to establish multiple linkages between frontal areas and specific limbic and sensory cortices through the posterior parietal cortex. The networks thus defined may form part of the neural substrate of parallel distributed processing in the cerebral cortex.

Animals↗
PubMed1989

Connections of the ventral granular frontal cortex of macaques with perisylvian premotor and somatosensory areas: anatomical evidence for somatic representation in primate frontal association cortex.

In macaque monkeys with injections of tritiated amino acids or horseradish peroxidase in the ventrolateral granular frontal cortex, we observed extensive anterograde and retrograde labeling of the premotor and somatosensory cortex in and around the lateral sulcus. Comparable labeling was not present with large and small control injections of the dorsal granular cortex. Cytoarchitectonic evaluation of the perisylvian cortex in the three cases examined in detail indicated that labeled areas included the ventral premotor cortex (area 6V); the precentral opercular and orbitofrontal opercular areas (PrCO and OFO); the second somatosensory area (S-II); the opercular cortex immediately anterior to S-II, possibly corresponding to area 2 of the S-I complex; and the central part of the insular cortex, including portions of the granular and dysgranular insular fields (Ig, Idg). Labeling was particularly dense and extensive in areas 6V, S-II, and OFO. Lighter labeling was also present in the rostral inferior parietal lobule (areas 7b and POa). The distribution of label within perisylvian areas was not uniform: certain parts were heavily labeled, while other parts were lightly labeled or unlabeled. Comparison of label distribution with published accounts of the somatotopy of these areas indicates that forelimb and orofacial representations were selectively labeled. Further, our results, taken together with other recent anatomical findings (e.g., Matelli et al.: Journal of Comparative Neurology 251:281-298, 1987; Barbas and Pandya: Journal of Comparative Neurology 256:211-228, 1987) suggest strongly that there is a network of interconnected forelimb and orofacial representations in macaque cortex, involving the ventral granular frontal cortex, area 6V, OFO, opercular area 2, S-II, the central insula, and area 7b. Each injection of frontal cortex which labeled the perisylvian somatic cortex involved the cortex of the ventral rim of the principal sulcus (PSvr). The cortex surrounding the PSvr does not stand out as a distinct area in Nissl-stained material. However, examination of myelin-stained sections prepared from uninjected hemispheres with the Gallyas technique revealed the existence of a distinct zone centered on the PSvr. This myeloarchitectonic area, which we term area 46vr, is more heavily myelinated than the ventral bank and fundus of the principal sulcus (area 46v) but is less heavily myelinated than the ventral (inferior) convexity (area 12). Involvement of area 46vr in our injections was probably responsible for the strong labeling observed in perisylvian somatic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1989

Quantitative autoradiographic mapping of serotonin 5-HT1 and 5-HT2 receptors and uptake sites in the neocortex of the rhesus monkey.

The in vitro autoradiographic technique was used to characterize the distribution of serotonin 5-HT1 and 5-HT2 receptors and uptake sites in 11 cortical areas of frontal, parietal, and occipital lobes in the rhesus monkey; 5-HT1 receptors were labeled with [3H]5-HT; 5-HT2 receptors were labeled with [3H]ketanserin; and 5-HT uptake sites were labeled with [3H]citalopram. Five-HT1 and 5-HT2 receptors and 5-HT uptake sites were found in every cortical area examined with the absolute concentration of 5-HT1 receptors higher than that of 5-HT2 receptors in all areas. In eight regions of prefrontal and parietal as well as in prestriate cortex, 5-HT1 and 5-HT2 receptors had complementary distribution profiles: 5-HT1 receptors were concentrated in layers I and II and the upper strata of layer III, while 5-HT2 receptors had their highest concentration throughout layers III and IV. Only the primary motor and visual cortex had receptor distributions different from that described above. Thus, in the primary visual cortex, both 5-HT1 and 5-HT2 receptors were found in high concentration in sublayer IVc beta, though the density of 5-HT1 receptor was also high in other subdivisions of layer IV and in layers III, V, and VI. In the primary motor cortex, both receptor subtypes were concentrated in layers I and II and the upper strata of layer III. The pattern of distribution of serotonin uptake sites did not match the patterns of distribution of either 5-HT1 or 5-HT2 receptors alone; rather it approximated the combined patterns of distribution of both receptor subtypes. The complementary patterns of distribution of 5-HT1 and 5-HT2 receptors in most areas of the monkey cerebral cortex suggest that these two receptor subtypes may make differential contributions to cortical functions.

Animals↗
PubMed1989

Comparison of human infants and rhesus monkeys on Piaget's AB task: evidence for dependence on dorsolateral prefrontal cortex.

This paper reports evidence linking dorsolateral prefrontal cortex with one of the cognitive abilities that emerge between 7.5-12 months in the human infant. The task used was Piaget's Stage IV Object Permanence Test, known as AB (pronounced "A not B"). The AB task was administered (a) to human infants who were followed longitudinally and (b) to intact and operated adult rhesus monkeys with bilateral prefrontal and parietal lesions. Human infants displayed a clear developmental progression in AB performance, i.e., the length of delay required to elicit the AB error pattern increased from 2-5 s at 7.5-9 months to over 10 s at 12 months of age. Monkeys with bilateral ablations of dorsolateral prefrontal cortex performed on the AB task as did human infants of 7.5-9 months; i.e., they showed the AB error pattern at delays of 2-5 s and chance performance at 10 s. Unoperated and parietally operated monkeys succeeded at delays of 2, 5, and 10 s; as did 12 month old human infants. AB bears a striking resemblance to Delayed Response, the classic test for dorsolateral prefrontal function in the rhesus monkey, and indeed performance on AB and Delayed Response in the same animals in the present study was fully comparable. These findings provide direct evidence that AB performance depends upon dorsolateral prefrontal cortex in rhesus monkeys and indicates that maturation of dorsolateral prefrontal cortex may underlie the developmental improvement in AB performance of human infants from 7.5-12 months of age. This improvement marks the development of the ability to hold a goal in mind in the absence of external cues, and to use that remembered goal to guide behavior despite the pull of previous reinforcement to act otherwise. This confers flexibility and freedom to choose and control what one does.

Aging↗
PubMed1989

Distribution of major neurotransmitter receptors in the motor and somatosensory cortex of the rhesus monkey.

The in vitro quantitative autoradiographic technique was used to characterize the distributions of alpha 1, alpha 2, beta 1 and beta 2 adrenergic, D1 and D2 dopaminergic, 5-HT1 and 5-HT2 serotonergic, M1 and M2 cholinergic, GABAA and benzodiazepine receptors in the motor (Brodmann's area 4) and somatosensory (Brodmann's areas 3, 1 and 2) cortex of the adult rhesus monkey. All receptor subtypes studied were present throughout all layers of both areas. In the somatosensory cortex, each receptor had its own laminar distribution. Some subtypes of the same receptor (5-HT1 and 5-HT2; alpha 1 and alpha 2) had complementary distributions while others (beta 1 and beta 2; D1 and D2; M1 and M2) had largely overlapping distributions. In contrast, different receptors had remarkably coincidental distributions in the motor cortex. In this area, they all tended to concentrate in layers I, II and the upper part of layer III. However, such coextensive distribution of many types of neurotransmitter receptors is not observed in motor cortex of rats and humans and therefore may be a distinctive feature of motor cortex in the rhesus monkey. The findings described in this paper indicate that somatosensory and motor areas are distinct in their receptor architecture and that receptor autoradiography provides a useful complement to classical histological techniques in elucidating areal differences in the cortex.

Animals↗
PubMed1989

Gonadal hormones influence the emergence of cortical function in nonhuman primates.

The role of gonadal hormones in the maturation of the orbital prefrontal cortex (ORB) was studied in normal male and female rhesus monkeys, monkeys given ORB lesions at 50 days of age, and female monkeys given androgen at different ages. Monkeys were tested on an object discrimination reversal task at 75 days of age. Gender influenced the performance of monkeys on the task during normal development and after ORB lesions. Normal males made fewer errors than did normal females. Females treated with androgen performed similarly to normal male monkeys. ORB lesions produced deficits in male monkeys and in females given androgen during late prenatal or early postnatal life, but not in normal females. These findings suggest that gonadal hormones may play an inductive role in the differentiation of higher cortical function in nonhuman primates.

Animals↗
PubMed1989

Dopamine D2 receptors in the cerebral cortex: distribution and pharmacological characterization with [3H]raclopride.

An apparent involvement of dopamine in the regulation of cognitive functions and the recognition of a widespread dopaminergic innervation of the cortex have focused attention on the identity of cortical dopamine receptors. However, only the presence and distribution of dopamine D1 receptors in the cortex have been well documented. Comparable information on cortical D2 sites is lacking. We report here the results of binding studies in the cortex and neostriatum of rat and monkey using the D2 selective antagonist [3H]raclopride. In both structures [3H]raclopride bound in a sodium-dependent and saturable manner to a single population of sites with pharmacological profiles of dopamine D2 receptors. D2 sites were present in all regions of the cortex, although their density was much lower than in the neostriatum. The density of these sites in both monkey and, to a lesser extent, rat cortex displayed a rostral-caudal gradient with highest concentrations in the prefrontal and lowest concentrations in the occipital cortex, corresponding to dopamine levels in these areas. Thus, the present study establishes the presence and widespread distribution of dopamine D2 receptors in the cortex.

Animals↗
PubMed1989

Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex.

Dopamine (DA)-containing projections to the cerebral cortex are considered to play an important role in cognitive processes. Using a recently developed monoclonal antiserum directed against DA and an antibody directed against tyrosine hydroxylase in combination with Golgi impregnation and electron microscopy, we have observed that DA and tyrosine hydroxylase afferents establish symmetric membrane specializations with the soma, dendritic shafts, and spines of identified pyramidal cells in the prefrontal, cingulate, and motor cortex of primates. The axospinous contacts invariably formed part of a synaptic complex in which the dendritic spine of a pyramidal neuron was the target of both a DA-positive symmetric and an unlabeled asymmetric bouton. This arrangement allows direct DA modulation of the overall excitability of cortical projection neurons by altering local spine responses to excitatory inputs.

Animals↗
PubMed1989

Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.

1. An oculomotor delayed-response task was used to examine the spatial memory functions of neurons in primate prefrontal cortex. Monkeys were trained to fixate a central spot during a brief presentation (0.5 s) of a peripheral cue and throughout a subsequent delay period (1-6 s), and then, upon the extinction of the fixation target, to make a saccadic eye movement to where the cue had been presented. Cues were usually presented in one of eight different locations separated by 45 degrees. This task thus requires monkeys to direct their gaze to the location of a remembered visual cue, controls the retinal coordinates of the visual cues, controls the monkey's oculomotor behavior during the delay period, and also allows precise measurement of the timing and direction of the relevant behavioral responses. 2. Recordings were obtained from 288 neurons in the prefrontal cortex within and surrounding the principal sulcus (PS) while monkeys performed this task. An additional 31 neurons in the frontal eye fields (FEF) region within and near the anterior bank of the arcuate sulcus were also studied. 3. Of the 288 PS neurons, 170 exhibited task-related activity during at least one phase of this task and, of these, 87 showed significant excitation or inhibition of activity during the delay period relative to activity during the intertrial interval. 4. Delay period activity was classified as directional for 79% of these 87 neurons in that significant responses only occurred following cues located over a certain range of visual field directions and were weak or absent for other cue directions. The remaining 21% were omnidirectional, i.e., showed comparable delay period activity for all visual field locations tested. Directional preferences, or lack thereof, were maintained across different delay intervals (1-6 s). 5. For 50 of the 87 PS neurons, activity during the delay period was significantly elevated above the neuron's spontaneous rate for at least one cue location; for the remaining 37 neurons only inhibitory delay period activity was seen. Nearly all (92%) neurons with excitatory delay period activity were directional and few (8%) were omnidirectional. Most (62%) neurons with purely inhibitory delay period activity were directional, but a substantial minority (38%) was omnidirectional. 6. Fifteen of the neurons with excitatory directional delay period activity also had significant inhibitory delay period activity for other cue directions. These inhibitory responses were usually strongest for, or centered about, cue directions roughly opposite those optimal for excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Resolution of metabolic columns by a double-label 2-DG technique: interdigitation and coincidence in visual cortical areas of the same monkey.

A double-label modification of the 2-deoxyglucose (DG) technique uses both 3H-2-DG and 14C-2-DG and allows for metabolic activity engaged by 2 distinct experimental conditions to be dissociated throughout the brain of a single subject. In the present study, we used this double-label method to examine the relationship between metabolic columns subserving the 2 eyes in cortical visual areas V1 and V2. The left and right eye's ocular dominance columns were separately activated in the same monkey to demonstrate that the double-label 2-DG method can resolve metabolic differences at the level of the cortical column. In 2 monkeys, 14C-2-DG was injected first and one eye was occluded while the other eye was visually stimulated for 30 min. Then 3H-2-DG was injected, and the occluder was switched so that the alternate eye was stimulated with the same pattern for 30 min. Autoradiographs depicting the 2 labels separately were obtained by exploiting the differential sensitivity of X-ray film and Ultrofilm to 3H and 14C emissions and by applying a radioactivity-subtraction algorithm to pairs of digitized images of the same section (Friedman et al., 1987). Columnar regions of increased activity were evident throughout V1, excepting the representations of the optic disk and monocular crescent. Superimposition of the 3H and 14C images from the same sections demonstrated that columns of increased 3H label were interdigitated with columns of increased 14C label in V1. In contrast, bands of increased 3H-2-DG uptake in extrastriate area V2 were largely coincident with the bands of increased 14C-2-DG uptake. These results illustrate the value of the double-label 2-DG technique for studying fluctuations of metabolic activity under different experimental conditions in the same subject. In the present example, the demonstration that ocular dominance columns are interdigitated in V1, whereas metabolically active bands are coincident in V2, would not have been fully appreciated by comparing 2-DG labeling across separate animals.

Animals↗
PubMed1988

Mediodorsal nucleus: areal, laminar, and tangential distribution of afferents and efferents in the frontal lobe of rhesus monkeys.

The terminal distribution of thalamic afferents in primate prefrontal cortex has never been examined in any detail. In the present study, WGA-HRP was injected into major subdivisions of the mediodorsal nucleus (MD) in the rhesus monkey in order to determine 1) The areal distribution of MD projections, 2) the layer(s) in which MD afferents terminate, 3) the tangential pattern of the MD axonal terminals, 4) the cells of origin of the reciprocal corticothalamic pathway, and 5) the degree of reciprocity between the corticothalamic and thalamocortical pathways in the different regions of the prefrontal cortex. As expected on the basis of retrograde degeneration and transport studies, injections centered in the magnocellular (MDmc) subnucleus of MD labeled cells and terminals in the ventral and medial prefrontal cortex. Injections involving ventral MDmc labeled the more lateral of these areas (Walker's areas 11 and 12); injections of the dorsal MDmc labeled the ventromedial regions (areas 13 and 14). In contrast, injections involving mainly the lateral, parvicellular (MDpc) moiety labeled cells and terminals in dorsolateral and dorsomedial areas (Walker's 46, 9, and 8B). Area 8A was labeled most prominently when injections included the multiform portion of MD (MDmf) and area 10 had connections with anterior portions of MD. A dorsal-ventral topography for MDpc exists with dorsal MDpc labeling dorsal and dorsomedial prefrontal areas and ventral MDpc labeling dorsolateral prefrontal cortex. Our findings with respect to MD are consistent with a nucleus-to-field organization of its thalamocortical projection system. Outside of the traditional boundaries of prefrontal cortex, lateral MD projections extended to the supplementary motor area (SMA) and the dorsal part of the anterior cingulate (AC) whereas the medial MD projection targeted the ventromedial cingulate cortex and spared SMA. In addition, a few labeled cells and sparse terminals were found in the inferior parietal lobule, the superior temporal sulcus, and the anterior part of the insula after injections that involved the medial part of MD. Labeled terminals were invariably confined to layer IV and adjacent deep layer III. No terminal label was ever observed in layers I, II, superficial III, V, or VI in any part of the cerebral cortex following injections confined to any part of MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1988

Regional distribution of cholecystokinin receptors in macaque medial temporal lobe determined by in vitro receptor autoradiography.

Cholecystokinin (CCK) binding sites were localized in the hippocampus, amygdala, and medial temporal cortices of macaque monkeys by using techniques of in vitro receptor autoradiography. Binding sites were labeled with 3H-CCK-8 and 125I-CCK-33, and nonspecific binding was assessed in the presence of 1 microM CCK-8. Comparison of autoradiograms with Nissl-stained sections allowed precise correlation of autoradiographic grain distribution with cytoarchitecture. CCK binding in the amygdala varied among nuclear subdivisions. It was dense in the lateral, basomedial, endopiriform, and cortical nuclei, in the parvicellular portion of the accessory basal nucleus, the periamygdaloid cortex, the cortical transition area, and in the amygdalohippocampal area. Labeling was sparse in the central, medial, and basolateral nuclei as well as in the magnocellular accessory basal nucleus. In the hippocampal formation, a single dense band of CCK binding was observed over the granule cell layer and adjacent few millimeters of the molecular layer of the dentate gyrus, while in the polymorph and remaining portions of this layer binding was of very low density. Prominent label over the pyramidal layer in the presubiculum clearly distinguished this region from the adjacent subiculum in which binding just exceeded background levels. Moderate to light label was observed in the hilus and stratum pyramidale of CA3, CA2, and CA1, while other hippocampal layers showed minimal specific binding. Variation in CCK binding in the medial temporal cortex showed close correspondence to cytoarchitectonic subdivisions. In entorhinal cortex, for example, binding was concentrated in layers III-VI while label in area 35 was prominent in all laminae except layer IV. Area TH of von Bonin and Bailey ('47) was distinguished from other regions by evenly distributed binding across all layers, while in area TF a bilaminar pattern of label in layers II and IV was observed. The highly specific patterns of CCK binding in amygdala and transitional cortices of the medial temporal lobe can be related to terminal fields of neo- and allocortical afferents to these regions, while label in the hippocampal formation coincides with the terminals of intrinsic neurons which ramify among the somata of cells that are targets of neocortical afferents. Thus, in all structures of the medial temporal lobe the disposition of peptidergic binding sites suggests that CCKergic systems may be important in the modulation of cortical afferents.

Amygdala↗
PubMed1988

Differential quenching and limits of resolution in autoradiograms of brain tissue labeled with 3H-, 125I- and 14C-compounds.

Problems in interpretation of autoradiograms generated by ligand binding in brain tissue may be caused by two types of technical limitations: the differential absorption of 3H-generated emissions within the tissue (differential quenching) and the reduced resolution when 125I and 14C are used as isotopes. In the course of our ongoing receptor binding studies in primate brain, we have examined these methodological problems using neocortex of adult rhesus monkey as an example of a complex multilayered brain structure. We have compared: (1) film images produced by brain sections mounted on 3H- and 14C-labeled plastic; (2) autoradiograms of sections labeled with pairs of similar compounds containing 3H, 125I or 14C; and (3) autoradiograms of normal and defatted brain sections. The results indicate that differential absorption of 3H-generated emissions presents a genuine problem for film autoradiography of neocortex of adult monkey when 3H-compounds are used. Particularly significant attenuations of 3H-generated emissions are associated with sublayer IVb of primary visual cortex (Brodmann's are 17) and layers III (deep strata), V and VI of primary motor cortex (Brodmann's area 4). This study provides the necessary corrections for autoradiographic measurements. We also found a loss of resolution associated with use of 125I and 14C, a result that poses a significant problem for analysis of fine laminar patterns of the neocortex in adult monkeys. The use of isotopes with high energy emissions tends to decrease the variations in optical densities within the autoradiograms of cortical sections. Thus, the variations in optical density of autoradiograms of cortices labeled with 125I- and 14C-compounds may not represent the true distribution of these compounds.

Animals↗
PubMed1988

Androgen binding and metabolism in the cerebral cortex of the developing rhesus monkey.

The influence of gonadal steroids on the maturation of the cerebral cortex and their possible influence on cortical function are not well understood. The present study examines androgen binding and metabolism in regions of the cerebral cortex and several subcortical structures at different time points during the development of the rhesus monkey. Androgen binding and metabolism were assessed in selected cortical and subcortical regions from neonatal, juvenile, and adult rhesus monkeys. Specific high affinity androgen-binding sites (apparent equilibrium dissociation constants for [3H]R1881, 0.04-0.3 nM) were observed in many areas of the rhesus monkey brain. These areas included (but were not limited to) the hypothalamus, amygdala, dorsolateral prefrontal cortex, orbital prefrontal cortex, visual and somatosensory cortex, and corpus callosum. Although the highest level of androgen binding was observed in the hypothalamus (8-20 fmol/mg protein), cortical samples also had measurable levels of binding (1-5 fmol/mg protein). No apparent regional or developmental differences in the number or affinity of androgen-binding sites were detected in animals ranging from 1 week to 8 yr in age. Androgen metabolism via aromatization and 5 alpha-reduction was observed in all regions of the neocortex examined, although at lower levels than in the hypothalamus and amygdala. Overall production of estrogens and 5 alpha-reduced androgens declined approximately 10-fold from prenatal to early postnatal life in both cortical and subcortical structures. The presence of androgen binding and metabolism in the monkey cerebral cortex indicates that steroid hormones may have considerable impact on cortical function in primates at postnatal as well as prenatal ages.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗