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P S Goldman-Rakic

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

At least 199 records · Page 11Linked to original sources
PubMed1982

Spatial memory impairments following damage to the mediodorsal nucleus of the thalamus in rhesus monkeys.

The present study assessed whether the mediodorsal nucleus (MD) of the primate thalamus subserves some of the same learning and memory functions mediated by its prefrontal cortical projection areas. Behavioral effects of MD lesions were evaluated in 14 young adult rhesus monkeys, using tests known to be sensitive to damage in different regions of the prefrontal cortex. Performance on a spatial delayed alternation task was significantly (P less than 0.01) impaired by MD lesions, and this impairment was significantly correlated (rs = 0.52) with damage to the posterior half of the mediodorsal nucleus. Such damage was also correlated significantly (rs = 0.51) with performance on another spatial memory task, delayed response; monkeys that sustained the largest lesions of the posterior mediodorsal nucleus were significantly (P less than 0.05) impaired on this task relative to operated animals suffering the least posterior MD damage. In contrast to their performance on spatial memory tasks, operated animals were not impaired on tests of object reversal or visual pattern discrimination. These results indicate that lesions of the mediodorsal nucleus can elicit a specific syndrome of spatial memory loss qualitatively similar to that observed after damage to the dorsolateral prefrontal cortex.

Animals↗
PubMed1982

Postnatal development of monoamine content and synthesis in the cerebral cortex of rhesus monkeys.

The concentration and rates of synthesis of norepinephrine, dopamine and serotonin were determined by spectrophotofluorometric methods in various cytoarchitectonic areas of the cerebral cortex in 54 rhesus monkeys ranging in age from 1 day to 36 months. For most regions studied, norepinephrine levels exhibit steady increases from birth through 36 months while over the same period changes in dopamine concentration are more complex and variable, particularly in the frontal lobe. Among the 3 monoamines examined, endogenous serotonin content shows the least dramatic and most rapid development, reaching adult values between 2 and 5 months of age in most cortical regions. As a consequence of these developmental shifts, the relationship of monoamine levels in various cortical areas also changes with age. At maturity, however, norepinephrine concentration exceeds that of dopamine and serotonin in the cortex of the frontal and parietal lobes whereas serotonin levels are higher than norepinephrine in the occipital cortex. Changes in rates of synthesis of the catecholamines and serotonin generally parallel developmental changes in concentrations. The greatest increments in catecholamine synthesis occur in prefrontal and posterior association cortices. Smaller but significant increases in serotonin metabolism were measured in the parietal and visual cortex between birth and 36 months while in other areas of the cortex, age-related changes in serotonin synthesis were negligible. A consistent finding at all ages is that the distribution of catecholaminergic synthesis varies inversely with that of serotonergic synthesis, indicating substantial interaction in the regulation of the two cortical systems. The present findings demonstrate that in the rhesus monkey development of monoaminergic storage capacity and synthetic processes: (1) continues over a period of months and years; (2) is generally more rapid for serotonin than for catecholamines; and (3) varies greatly in different cytoarchitectonic regions of the cerebral cortex.

Aging↗
PubMed1981

Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys.

To elucidate the anatomical relationships between the frontal association cortex and the limbic system in primates, projections from the amygdala to frontal cortex were studied in the rhesus monkey using retrograde and anterograde tracing methods. Following injections of horseradish peroxidase (HRP) into the orbital prefrontal cortex, the gyrus rectus, the superior frontal gyrus, and the anterior cingulate gyrus of the frontal lobe, labeled neurons were found in the basolateral, basomedial, or basal accessory nuclei of the amygdala. None of these nuclei contained labeled neurons following HRP injections into the principal sulcus or the lateral inferior convexity of the frontal lobe. This selective distribution of amygdala connections was confirmed by injection tritiated amino acids into the amygdala. Silver grains were present only over the orbital cortex and gyrus rectus on the ventral surface of the frontal lobe and over the superior prefrontal gyrus and anterior cingulate gyrus on the medial wall of the hemisphere, while the dorsolateral prefrontal cortex was free of radioactivity. The isotope injection of the amygdala also revealed a projection to the magnocellular moiety of the mediodorsal nucleus (MDmc) which is known to innervate the same ventromedial regions of the frontal lobe that receive direct connections from the amygdala. Although MDmc and amygdala project to the same cortical regions, their terminal fields are different. The direct amygdala input terminates in layer 1 in orbital cortex and gyrus rectus and layer 2 in the dorsomedial cortex and cingulate gyrus, while the thalamic input is primarily to layer 3 and, in some areas, also the superficial half of layer 1. These findings indicate that the frontal lobe of rhesus monkeys can be subdivided into two separable cortical regions: 1) A ventromedial region including the anterior cingulate gyrus which receives both direct (amygdalo-cortical) and indirect (amygdalo-thalamo-cortical) input from the amygdala; and 2) a dorsolateral frontal region which is essentially devoid of either direct or indirect amygdalofugal axons. On the basis of its selective relationship with the amygdala, the ventromedial region may be considered the "limbic" portion of the frontal association cortex.

Amygdala↗
PubMed1981

Prenatal formation of cortical input and development of cytoarchitectonic compartments in the neostriatum of the rhesus monkey.

The timing, hemispheric laterality, and mode of termination of input from the prefrontal association cortex to the neostriatum were studied in fetal and neonatal rhesus monkeys using autoradiography for tracing connections. In addition, the cytological maturation of the neostriatum was examined in Nissl-stained sections from the same and other monkeys of selected prenatal and postnatal ages. A small contingent of corticostriatal axons reaches both the caudate nucleus and the putamen by the 69th embryonic day (E69) of the 165-day gestation period in this species and steadily expands over the next 3 fetal months. Throughout this period, ipsilateral perfrontostriatal connections predominate, and only a small and variable amount of label is detectable over the contralateral neostriatum. A major feature of the developing corticostriatal projection is a transfiguration in the distribution of its terminals: from E69 to E95, cortical terminals are distributed uniformly among neostriatal neurons; beginning around E105, areas of higher and lower grain density begin to emerge until finally, by E133, 250- to 500-micrometers-wide circular and elliptically shaped label-free cores perforate a field of densely labeled cortical terminals as in the neostriatum of the adult monkey (Goldman, P. S., and W. J. H. Nauta (1977) J. Comp. Neurol. 171: 369-386). The cytoarchitectonic composition of the neostriatum also changes during gestation: from E69 through E95, the small postmitotic neurons of the immature neostriatum are packed densely and, for the most part, are distributed homogeneously; by E105, they become segregated into cellular islands consisting of densely packed neurons that are encapsulated by fiber-rich annuli and embedded in a matrix of less densely arrayed neurons. The shape and size of the islands in Nissl-stained sections correspond to label-free cores in autoradiograms of fetuses with cortical injections, while the surrounding annuli and adjacent matrix cells correspond to areas of dense accumulation of label. Thus, the formation of the corticostriatal projection in primates involves a transformation in the distribution of ingrowing terminals synchronized with changes in cellular organization of the neostriatum.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Estrogen formation in the mammalian brain: possible role of aromatase in sexual differentiation of the hippocampus and neocortex.

Recent studies suggest that sex differences in cognitive function may involve effects of circulating androgens on the developing cerebral cortex and hippocampus. The mechanism of these effects is not understood. In rhesus monkeys, aromatase activity is present in the hippocampus and several areas of the cerebral cortex during late fetal and early postnatal life. Similarly, work in rats and mice indicates that the hippocampus and cerebral cortex may be capable of estrogen biosynthesis during early development. These results are consistent with the hypothesis that the actions of androgens on the developing cerebral cortex and hippocampus may involve local estrogen-mediated effects similar to those responsible for differentiation of the hypothalamic mechanisms controlling reproductive function.

Animals↗
PubMedDate not supplied

Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys.

The administration of alpha-2 adrenergic agonists to aged monkeys has been shown to ameliorate their cognitive deficits on the delayed response (DR) task, a test of spatial working memory (3,5). The present experiment tested whether the alpha-2 agonists, clonidine and guanfacine, would also improve working memory for object feature recognition, as tested by the delayed nonmatch-to-sample (DNMS) task. Five aged monkeys were trained on DNMS and were found to have mild performance deficits comparable to those reported previously for monkeys of similar age (32). However, during the subsequent two years of drug testing, the animals' baseline performance steadily improved, and conditions had to be made progressively more difficult to produce errors in performance. Clonidine and guanfacine significantly altered the DNMS performance of the aged monkeys, but drug-induced improvement was not as robust for DNMS as it was for DR. Clonidine produced a triphasic dose/response curve: Impairment was observed at both very low and high doses, while modest improvement was seen in the middle dose range (average maximal improvement of 21 +/- 2.4%). Although improvement could occasionally be replicated for some doses, the clonidine dose/response curves were remarkably inconsistent in the middle dose range. Similarly, doses of guanfacine which had previously produced optimal improvement on the DR task, produced only small but significant improvement in DNMS performance (average improvement of 11 +/- 3% for the 0.00011-0.000011 mg/kg dose range).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Interhemispheric integration: I. Symmetry and convergence of the corticocortical connections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) in the rhesus monkey.

The relationship between the termination zones of projections from paired homotopic areas in the frontal lobe was examined in the cerebral cortex of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the cortical regions that received bilateral inputs from these areas were processed for the respective tracers, permitting the relationship between the converging projections to be defined. Comparison of the cortical connections of the left and right PS or of the left and right SMA yielded two major findings. First, only minor differences in the topographic distribution and strength of connections of homotopic areas were observed, providing little evidence of asymmetry in the connections of either the PS or the SMA in the macaque. Second, with the exception of interdigitation observed in a portion of the dorsal bank of the PS, the cortical projections from both the left and the right PS and SMA converged (overlapped) in common columnar territories. These termination patterns allow for a remarkable degree of interhemispheric integration.

Animals↗
PubMedDate not supplied

Interhemispheric integration: II. Symmetry and convergence of the corticostriatal projections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) of the rhesus monkey.

The relationship between the termination zones of projections from paired homotopic areas of the frontal lobes was examined in the caudate nucleus and the putamen of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or of the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the neostriatum were processed for the respective tracers, permitting the relationship between the converging projections to be defined. The topographic distribution and strength of ipsilateral corticostriatal projections observed for separately labeled left and right hemispheres were strikingly similar. Projections from the left and the right PS terminated preferentially in central parts of the left and right neostriata, respectively, while projections of the left and right SMAs terminated preferentially in dorsolateral parts of respective left and right neostriata. Therefore, little evidence for asymmetry of corticostriatal projections was found. The projections of the left and the right PS to the same neostriatum were also compared. Remarkably, whether in the left or right hemisphere, projections from the left and the right PS were in precise register in topographically specific territories of the caudate and putamen. Likewise, projections of the left and right SMAs converged in both the left and right neostriata. Such convergence allows for a remarkable degree of interhemispheric integration in the descending corticostriatal networks.

Animals↗
PubMedDate not supplied

Low-affinity nerve growth factor receptor (p75NGFR)- and choline acetyltransferase (ChAT)-immunoreactive axons in the cerebral cortex and hippocampus of adult macaque monkeys and humans.

Low-affinity nerve growth factor receptor (p75NGFR) was analyzed in the adult monkey and human cerebral cortex and hippocampus by light and electron microscopic immunohistochemistry using a mouse monoclonal antibody raised against human p75NGFR. In the monkey only, the morphology and laminar and areal distribution of the p75NGFR-immunoreactive fibers were further compared with distribution of the ACh-synthesizing enzyme ChAT. We found that the p75NGFR fiber distribution is remarkably dense throughout the cerebral neocortex and highly similar in homologous cortical areas of monkey and human. In both species, p75NGFR-immunoreactive fibers are contracted in layers I, II, and the superficial portions of layer III in all frontal, parietal, temporal, and occipital areas examined. In the primary visual and somatosensory cortices, dense p75NGFR fiber plexuses are additionally found in layer IV. In the hippocampal formation, this fiber system is most dense in the CA2 and CA3 subfields as well as in the molecular and polymorphic layers of the dentate gyrus. The distribution and characteristics of the p75NGFR-positive fibers in the primates correspond almost exactly to those of the cholinergic fiber system as revealed by ChAT immunohistochemistry in the present study as well as in the literature (Lewis, 1991; Mesulam et al., 1992; Voytko et al., 1992). Electron microscopy revealed that p75NGFR is associated mainly with axonal membranes and portions of the axoplasm in labeled fibers. Although the function of p75NGFR is still a matter of debate, its widespread distribution opens up new questions regarding its physiological role in the large and functionally differentiated cerebral cortex and hippocampus of monkey and human.

Adult↗
PubMedDate not supplied

Characterization of the dopaminergic innervation of the primate frontal cortex using a dopamine-specific antibody.

The mesencephalic dopaminergic system has been implicated in the motor and cognitive operations of the cerebral cortex as well as in the pathogenesis of neurological and psychiatric disorders. However, to date, the dopamine (DA)-containing axons of the primate cerebral cortex have not been directly visualized immunohistochemically due to the lack of a DA-specific antibody. We have now analyzed the regional and laminar distribution of DA-immunoreactive (DA-IR) afferents in the frontal cortex of the rhesus monkey using a monoclonal antibody specific for DA. In addition, we compared the distribution of DA-IR processes to tyrosine hydroxylase (the rate-limiting enzyme in DA synthesis) immunoreactive (TH-IR) axons. Frontal cortex displays an elaborate and robust dopaminergic innervation. Although regional differences in the DA-IR innervation were clearly evident, variations in the DA innervation were essentially unrelated to cytoarchitectonic boundaries. Instead, the DA innervation followed two basic gradients: (1) a prominent medial-to-lateral gradient of decreasing fiber density that was most prominent in the dorsal cortical regions, and (2) a more subtle anterior-posterior gradient in which DA-IR fiber density decreased slightly in both rostral and caudal directions from a peak density centered in the region of granular frontal area 8Bm and the supplementary motor area 6M. The laminar pattern of DA-IR axons also showed regional variations that again were typified by smooth transitions irrespective of cytoarchitecture. Analysis of DA-IR axonal morphology indicated that immunoreactive fibers form a basically uniform population, giving little evidence of a bimodal heterogeneity evident in other species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Heterogeneous targets of dopamine synapses in monkey prefrontal cortex demonstrated by serial section electron microscopy: a laminar analysis using the silver-enhanced diaminobenzidine sulfide (SEDS) immunolabeling technique.

Dopamine projections to the cerebral cortex have been implicated in normal and pathological cognitive processes, notably, Parkinson's disease and schizophrenia. To help elucidate the function of these dopamine axons, they were characterized by serial section electron microscopy in individual layers of monkey prefrontal cortex. Dopamine immunoreactivity was visualized with a silver precipitation technique that allowed clear resolution of the internal structures and cell membranes of labeled axons. Apart from the occasional large microtubule-filled axon, dopamine axons were thin and varicose with many clear synaptic vesicles and fewer dense-core vesicles. With few exceptions, dopamine synapses were symmetric and quite small, seen in only one to three serial sections. A determination of the "synaptic incidence" showed that only 39% of labeled varicosities formed identifiable synapses. However, it is certain that some small synapses could not be visualized even in serial sections, and it is possible that the vast majority if not all varicosities form synapses. Except for one soma, dendritic spines and shafts were the recipients of dopamine synapses. Many postsynaptic shafts were small and spiny, indicating that they were distal pyramidal dendrites. However, some postsynaptic shafts especially in supragranular layers had distinctly nonpyramidal features. These lacked spines, had a high density of synaptic inputs, and often had a strikingly varicose morphology. The data suggest that the majority of dopamine synapses in all layers are on pyramidal cells, but that a significant fraction are on presumed GABAergic nonpyramidal cells.

3,3'-Diaminobenzidine↗
PubMedDate not supplied

Synaptogenesis in the prefrontal cortex of rhesus monkeys.

Since the turn of the century, the prefrontal association areas of the cerebral cortex have been thought to be among the last regions of the cortical mantle to develop. We have examined the course of synaptogenesis in the macaque prefrontal cortex by quantitative electron microscopic analysis in 25 rhesus monkeys ranging in age from embryonic day 47 (E47) to 20 years of age. A series of overlapping electron micrographs spanning the whole cortical thickness in each animal provided data on the number, the proportion, and the density of synapses per unit area (NA) and per unit volume (NV) of neuropil. The tempo and kinetics of synapse formation in prefrontal cortex closely resemble those described for sensory and motor areas, particularly during the stages of synapse acquisition and overproduction (Rakic et al., 1986). In young embryos, we describe a precortical phase (E47-E78), when synapses are found only above and below, but not within, the cortical plate. Following that, there is an early cortical phase, from E78 to E104, during which synapses accumulate within the cortical plate, initially exclusively on dendritic shafts. The next rapid phase of synaptogenesis begins at 2 months before birth and ends approximately at 2 months after birth, culminating with a mean density of 750 million synapses per cubic micrometer. This accumulation is largely accounted for by a selective increase in axospine synapses in the supragranular layers. The period of explosive synaptic density is followed by a protracted plateau stage that lasts from 2 months to 3 years of age when synaptic density remains relatively constant. The final period of decline, from 3 years through over 20 years of age, is marked by a slight but statistically significant decline in synaptic density. Concurrent recruitment of synapses with that of sensory and motor areas supports the concept that the initial establishment of cortical circuitry is governed by general mechanisms common to all areas, independent of their specific functional domain. The finding that synaptic density is relatively stable from early adolescence through puberty (the plateau period) is indicative of the importance, in primates, of a consistent and high synaptic density during the formative years when learning experiences are most intense.

Aging↗
PubMedDate not supplied

Cytoarchitectonic definition of prefrontal areas in the normal human cortex: I. Remapping of areas 9 and 46 using quantitative criteria.

The classical cytoarchitectonic maps of human prefrontal areas produced by various cartographers in the early part of this century, though similar in gross topography, differ from one another in their descriptions of the size, shape, and precise location of specific regions within the frontal promontory. The current advances in human neurobiology stimulated us to reinvestigate the cytoarchitecture of the human prefrontal cortex, beginning with areas 9 and 46, to establish a set of objective cytometric criteria for identification of these areas. Nisslstained and Gallyas-stained celloidin-embedded sections were prepared from the left hemispheres of 17 human subjects 23-73 years old, without history of neurological disease. In eight cases, light microscopic observations were supplemented by morphometric data collected on a research microscope equipped with differential interference contrast optics and interfaced to a TV monitor with video mixing equipment and a microcomputer. We used the three-dimensional counting method of Williams and Rakic (1988) to measure (1) total cortical and relative laminar thickness, (2) neuronal packing density per 0.001 mm3 in individual cortical layers, and (3) sizes of neuronal somata in selected cortical layers. Light microscopic analysis confirmed that the cortical layers are more differentiated in area 46 than in area 9, particularly at the borders of layer IV. Layers III and V exhibit clearer sublamination in area 9, while layer IV is also somewhat wider in area 46 than in area 9 (9.3% vs 6.4% of cortical thickness); the overall thickness of the cortex is the same in both areas. Cytometric analysis revealed that layer IV neurons of area 46 are more densely packed than those in area 9 (55.38 +/- 7.26 vs 45.80 +/- 4.45 neurons/0.001 mm3), as are neurons in the supragranular layers II and III combined (53.51 +/ 6.33 vs 45.69 +/ 3.81 neurons/0.001 mm3). Finally, neurons in area 46 are more homogeneous in size than those in area 9. Differences in myeloarchitecture are also evident: each area contains numerous, well-stained radial striae and two pronounced bands of horizontal fibers, but in general, area 46 is less myelinated than area 9. Objective cytometric methods can clearly distinguish two adjacent areas within the human prefrontal lobe. These findings may prove useful in the areal parcellation of the human cerebral cortex as well as provide a baseline for analysis of pathological changes in neurological and psychiatric disorders such as a schizophrenia, Huntington's or Alzheimer's diseases.

Adult↗
PubMedDate not supplied

Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. Variability in locations of areas 9 and 46 and relationship to the Talairach Coordinate System.

The human prefrontal cortex can be divided into structurally and functionally distinct cytoarchitectonic areas, but the extent of individual variation in the position, size, and shape of these areas is unknown. Using criteria described in the preceding companion article (Rajkowska and Goldman-Rakic, 1995), as well as visual inspection, we have mapped areas 9 and 46 in the frontal lobe of seven postmortem human brains, and completely reconstructed these dorsolateral regions in five of the seven cases. The lateral reconstructions in these five cases were analyzed and superimposed on the lateral view of the Talairach and Tournoux (1988) coordinate system in such a way as to render both the variability and the regions of overlap for the two prefrontal areas in the five different brains. Based on this exercise, we developed a set of conservative Talairach coordinates to define area 9 and 46. Area 9 is located on the dorsal, lateral, and dorsomedial surfaces of the frontal lobe extending along the middle third of the superior frontal gyrus and adjacent portions of the middle frontal gyrus in all cases examined. Area 46 lies on the dorsolateral convexity and is either partially or completely surrounded by area 9. It is consistently found on one or more convolutions of the middle frontal gyrus. The superior border of area 46 with adjacent cortex is also variable within the middle and superior frontal sulci, as is the inferior border within the upper wall of the inferior frontal sulcus. The genuine variability in the morphology of the human frontal lobe indicated by our findings suggests that the differences among the classical maps of Brodmann, von Economo and Koskinas, and Sarkissov and others may have been due to normal variation among the brains they analyzed. Such variation may underlie individual differences in the visuospatial and cognitive capacities subserved by these areas.

Adult↗