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P S Goldman-Rakic

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

At least 109 records · Page 6Linked to original sources
PubMed1993

Prefrontal connections of medial motor areas in the rhesus monkey.

Several areas on the medial surface of the frontal lobe in both monkeys and humans, including the supplementary motor area and specific areas within the ventral bank of the cingulate sulcus called the cingulate motor areas, have been implicated in the initiation and execution of skilled movements. These areas project directly to the motor cortex and spinal cord, and, on this basis alone, can be considered premotor areas. The present study investigated whether these premotor areas are specific targets of prefrontal cortical projections in the rhesus monkey and thereby provide links between this association cortex and motor effector pathways. Circumscribed injections of wheat germ agglutinin-conjugated horseradish peroxidase were placed into different cytoarchitectonic subdivisions of prefrontal cortex, and resultant retrograde and anterograde labeling examined with respect to designated premotor targets. Conversely, injections were also made in the supplementary and cingulate motor areas and labeled cells and terminals charted in the prefrontal cortex. A principal finding in this study is the identification of multiple prefrontal regions that project to the supplementary motor area, the cingulate motor areas, or both. Areas 46, 8a, 9, 11, and 12 are reciprocally connected with an area of the superior frontal gyrus in or near the supplementary motor area at its rostral margin. A smaller constellation of prefrontal areas, areas 46, 8a, and 11, is reciprocally connected with portions of cingulate cortex that have been classified as premotor arm and/or leg representations (Hutchins et al., Exp Brain Res 71:667-672, 1988). In accordance with numerous previous reports, prefrontal areas 46, 8a, 9, 10, 11, and 12 are reciprocally connected with "nonmotor" subdivisions of cingulate cortex. The results presented here specify the corticocortical connections by which prefrontal cortex may influence motor output.

Animals↗
PubMed1993

Dissociation of object and spatial processing domains in primate prefrontal cortex.

Areas and pathways subserving object and spatial vision are segregated in the visual system. Experiments show that the primate prefrontal cortex is similarly segregated into object and spatial domains. Neurons that code information related to stimulus identity are dissociable, both by function and region, from those that code information related to stimulus location. These findings indicate that the prefrontal cortex contains separate processing mechanisms for remembering "what" and "where" an object is.

Animals↗
PubMed1993

Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission.

Muscarinic m1 receptors traditionally are considered to be postsynaptic to cholinergic fibers, while m2 receptors are largely presynaptic receptors associated with axons. We have examined the distribution of these receptor proteins in the monkey cerebral cortex and obtained results that are at odds with this expectation. Using immunohistochemistry with specific antibodies to recombinant m1 and m2 muscarinic receptor proteins, we have demonstrated that both m1 and m2 receptors are prominently associated with noncholinergic asymmetric synapses as well as with the symmetric synapses that characterize the cholinergic pathways in the neocortex. At asymmetric synapses, both m1 and m2 receptor immunoreactivity is observed postsynaptically within spines and dendrites; the m2 receptor is also found in presynaptic axon terminals which, in the visual cortex, resemble the parvicellular geniculocortical pathway. In addition, m2 labeling was also found in a subset of nonpyramidal neurons. These findings establish that the m2 receptor is located postsynaptically as well as presynaptically. The association of m1 and m2 receptors with asymmetric synapses in central pathways, which use excitatory amino acids as neurotransmitters, provides a morphological basis for cholinergic modulation of excitatory neurotransmission.

Acetylcholine↗
PubMed1993

Neurochemical development of the hippocampal region in the fetal rhesus monkey. I. Early appearance of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex during the first half of gestation (E47 to E90).

Although the entorhinal cortex is a key structure connecting the hippocampal formation with the rest of the cerebral cortex, little is known about its early chemoanatomical development in primates. In the present study, a cytoarchitectonic analysis and immunocytochemical detection of somatostatin, neurotensin, parvalbumin, calbindin-D 28K, DARPP-32, as well as tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin, were carried out on serial sections of the entorhinal cortex of six rhesus monkey fetuses aged E47 to E90 (gestation period 165 days). At E56 the cortical plate of the entorhinal cortex already exhibited a sublamination; at E64 the lamina dissecans was partly formed, allowing the emergence of the lamina principalis externa and interna, and at E83 most of the regional and laminar subdivisions characteristic of the adult cortex could be identified, except for the rhinal sulcus restricted to a small dimple. The neurochemical development paralleled the early cytoarchitectonic differentiation, both largely preceding that of the neighboring cortical areas. The somatostatin-like immunoreactive innervation, first detected at E56, was very dense as early as E64 and displayed by E83 a laminar distribution similar to that found in the adult. Labeled neurons indicated an intrinsic origin for this innervation but an extrinsic connection might be present as labeled fibers in the subplate of the entorhinal cortex were in continuity with positive fibers in the intermediate zone of the hippocampal formation. A faint neurotensin-like immunoreactivity first detected at E64 became prominent at E83 in the entorhinal cortex but stopped abruptly at the anlage of the rhinal sulcus. The lack of neurotensin-labeled neurons contrasted with their presence in other parts of the hippocampal region and suggested a precocious extrinsic connection. Only rare parvalbumin-LIR neurons were detected at midgestation, whereas calbindin-D 28K was expressed from E47 on in Cajal-Retzius cells and from E56 on in various types of neurons in the cortical plate and subplate. Most characteristic was a category of medium-sized, deeply stained calbindin-LIR neurons, present only in the lamina principalis externa and possibly corresponding to the population of large neurons described by Kostovic et al. (1990, Soc Neurosci Abstr 16:846) in early developing entorhinal cortex of human fetuses. These and probably other neurons were also DARPP-32-positive, suggesting the possibility of an early dopaminergic regulation. Indeed, the monoaminergic innervation of the entorhinal cortex was detected from E56 on and gradually increased in density, displaying areal and laminar differences in the distribution of the dopaminergic, noradrenergic, and serotoninergic afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

In vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate.

There is an acute interest in studying the functional characteristics of dopamine systems in the cortex of primates. In particular, the prefrontal cortical dopamine projections have received a great deal of attention. This system is essential for proper functioning of the prefrontal cortex, and dysfunction within the system may be involved in some psychiatric and neurological illnesses. In vivo assessments of cortical dopamine in the primate have been scarce. This has been due, in part, to technical difficulties associated with these studies and with quantifying the relatively low levels of dopamine found in cortical regions. In the present study, intracerebral microdialysis was utilized to assess the extracellular concentration of dopamine in cortical and subcortical areas of the pentobarbital-anesthetized rhesus monkey. Basal extracellular dopamine levels were consistently detected in the medial prefrontal cortex, premotor cortex, and caudate-putamen. The basal extracellular concentration of dopamine in the dorsolateral prefrontal cortex was reliably detected in 1 of 4 animals. Intravenous administration of amphetamine (1 mg/kg) enhanced extracellular dopamine levels in the caudate-putamen area by more than 20-fold. In cortical areas, amphetamine's effect was less profound: An increase of 400-500 percent over basal extracellular dopamine levels was observed in each region. These studies demonstrate the feasibility of microdialysis for detecting extracellular fluxes of dopamine in the cortex of nonhuman primates. They further provide direct evidence that the dopamine released within the prefrontal cortex and the premotor cortex of nonhuman primates responds to pharmacological manipulation.

Amphetamine↗
PubMed1993

Silver-enhanced diaminobenzidine-sulfide (SEDS): a technique for high-resolution immunoelectron microscopy demonstrated with monoamine immunoreactivity in monkey cerebral cortex and caudate.

A common frustration of immunoelectron microscopy (IEM) is the density of the 3,3'-diaminobenzidine (DAB) label, which obscures intracellular details of labeled structures. To overcome this problem, a silver enhancement protocol was developed which leaves silver deposits on very low levels of DAB. The resulting label is composed of easily visualized punctate silver deposits, localized in processes with little or no detectable DAB. This technique incorporates several modifications into previously described methods for silver enhancement of DAB. The principal innovation is to pretreat the DAB label with sodium sulfide before silver enhancement, which substantially increases the sensitivity of the silver enhancement. In addition, cysteine was used in place of thioglycolic acid to suppress tissue argyrophilia, allowing use of both glutaraldehyde- and paraformaldehyde-fixed tissue without degradation of ultrastructure. We demonstrate this technique with dopamine, norepinephrine (NE), and serotonin (5HT) immunoreactivity in monkey prefrontal cerebral cortex and with dopamine immunoreactivity in the anterior caudate. The punctate label allows essentially unobscured visualization of the intracellular details and cell membranes of these monoamine axons. Whereas 5HT axons formed small asymmetric synapses, dopamine and NE axons typically formed small symmetric synapses with notably subtle membrane specializations. It is likely that these are often obscured by conventional DAB labeling. The use of several preparations indicates that this technique will be useful with a variety of antibodies. It might also provide an attractive alternative to colloidal gold, especially with glutaraldehyde-fixed tissue which is not easily penetrated by gold particles.

3,3'-Diaminobenzidine↗
PubMed1993

Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas".

The spatial memory functions of the monkey's prefrontal cortex were examined with oculomotor delayed-response (ODR) paradigms that required the animal to remember the spatial location of peripheral visual cues, while maintaining fixation on a central visual target during the presentation of each cue and during a subsequent 1.5-8 sec delay period. Four rhesus monkeys received unilateral or serial prefrontal lesions in and around the principal sulcus after they reached criterion performance on the ODR tasks. Unilateral lesions disrupted the performance of memory-guided eye movements to spatial cues in the visual field contralateral to the hemisphere in which the lesion was placed. Memory-guided eye movements to ipsilateral cues were mildly affected by unilateral lesions, and these lesions had little or no effect on performance in visually guided control tasks. With addition of a second lesion in the opposite hemisphere, the deficit was extended to include the opposite hemifield. The impairment was characterized by eye movements of inappropriate direction, and, excepting the one lesion that extended into the frontal eye field region of the arcuate sulcus, saccadic reaction times and velocities were the same before and after the lesions. The effect of the lesions was delay dependent: performance was rarely altered at the shortest (1.5 sec) delay but became progressively worse as the delay period was lengthened. The present results strengthen the evidence that the delayed-response deficits of monkeys with prefrontal lesions are caused by failure to maintain a transient memory "trace" in working memory, and indicate for the first time that working memory mechanisms are lateralized: memories for visuo-spatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. These findings provide evidence for the concept of mnemonic hemianopias and mnemonic scotomas, that is, memory deficits for particular hemifields or visual field locations, unaccompanied by simple sensory or motor deficits.

Animals↗
PubMed1992

Acetylcholinesterase reactivity in the frontal cortex of human and monkey: contribution of AChE-rich pyramidal neurons.

Light and electron microscopic histochemistry were used to analyze the distribution of the enzyme acetylcholinesterase (AChE) in the frontal cortex of macaque monkey and human. In prefrontal, premotor, prelimbic, and medial paralimbic areas, AChE reactivity showed a characteristic bilaminar appearance due to a combination of positive neuronal and fiber labeling in deep layer III and layer V. In addition, layer I contained dense AChE-reactive fiber plexuses labeled throughout the frontal areas. One of the major issues addressed in this study was whether pyramidal neurons in the nonhuman primate cortex express AChE reactivity, as has been reported for humans. Three different histochemical methods were applied to provide confidence in the reliability of the results. Light microscopic analysis revealed strongly reactive, intensely stained pyramidal neurons in monkey as well as in the human. Further, these AChE-rich neurons exhibited the same pattern of laminar and regional variation in both species. In the prefrontal and premotor areas, AChE-rich pyramidal neurons predominated in layer III. In the motor cortex, they were also concentrated in layer III, but numerous AChE-rich pyramids were observed in layer V. In contrast, medial paralimbic areas had more AChE-rich neurons in layer V than in layer III. Finally, at the electron microscopic level, the subcellular distribution of AChE histochemical product in pyramidal neurons was identical in both monkey and human. The only difference noted between the two species was that the density of AChE-rich pyramidal neurons was greater in humans than in monkeys. Since nonhuman primates possess a system of AChE-reactive pyramidal neurons similar to human, they provide a potentially useful animal model for analyzing acetylcholinesterase neuronal systems in the cortex, which are compromised in various neuropathological diseases like Alzheimer's disease.

Acetylcholinesterase↗
PubMed1992

Light and electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex.

The distribution and synaptic connections of dopamine axons were studied by light and electron microscopy in human cerebral cortex. For this purpose, dopamine immunoreactivity was characterized in apparently normal anteriolateral temporal cortex, which was removed to gain access to the medial temporal lobe during tumor excision or treatment of epilepsy. Nissl sections showed this to be granular neocortex. Dopamine fibers were distributed throughout this cortex, although there were relatively more fibers in layers I-II and in layers V-VIa, compared to layers III-IV and VIb, resulting in a bilaminar pattern of labeling. In all layers, fibers were seen to form numerous varicosities, and to vary in size from thick to very fine. Fibers were relatively straight, sparsely branched and were oriented in various planes within the cortex. However, in layer I, they often ran parallel to the pial surface. In order to analyze the functional interactions of dopamine fibers, individual cortical layers were surveyed for dopamine synapses. These were usually symmetrical (Gray's type II), although 13% of them were asymmetrical. Approximately 60% of dopamine synapses were made with dendritic spines, and 40% with dendritic shafts, and this ratio was similar in all layers. On both spines and shafts, it was common to see dopamine synapses closely apposed to an unlabeled asymmetric input, suggesting a dopamine modulation of excitatory input. Some postsynaptic dendritic shafts had features of pyramidal cells, including formation of spines. Since pyramidal cells are the major type of cortical spiny neuron, they probably represent the main target of dopamine synapses in this cortex. There were also dopamine profiles apposed to membrane densities on unlabeled axon terminals, suggesting another type of synaptic interaction. These findings provide the first documentation of dopamine synapses in the human cortex, and show that they form classical synaptic junctions. The location of these synapses on spines and distal dendrites, and their proximity to asymmetric synapses, suggest a modulatory role on excitatory input to pyramidal cells.

Axons↗
PubMed1992

The synaptology of parvalbumin-immunoreactive neurons in the primate prefrontal cortex.

Electron microscopy and immunocytochemistry with a monoclonal antibody against parvalbumin (PV) were combined to analyze the distribution and morphology of PV-immunoreactive (PV-IR) neurons and the synaptology of PV-IR processes in the principal sulcus of the macaque prefrontal cortex. Parvalbumin-IR neurons are present in layers II-VI of the macaque principal sulcus (Walker's area 46) and are concentrated in a band centered around layer IV. PV-IR cells are exclusively non-pyramidal in shape and are morphologically heterogeneous with soma sizes ranging from less than 10 microns to greater than 20 microns. Well-labeled neurons that could be classified on the basis of soma size and dendritic configuration resembled large basket and chandelier cells. A novel finding is that supragranular PV-IR neurons exhibit dendritic patterns with predominantly vertical orientations, whereas infragranular cells exhibit mostly horizontal or oblique dendritic orientations. PV-IR cells within layer IV exhibit a mixture of dendritic arrangements. Vertical rows of PV-IR puncta, 15-30 microns in length, resembling the "cartridges" of chandelier cell axons were most dense in layers II, superficial III, and the granular layer IV but were not observed in the infragranular layers. Cartridges were often present beneath unlabeled, presumed pyramidal cells. PV-IR puncta also formed pericellular nests around pyramidal cell somata and proximal dendrites, suggestive of basket cell innervation. PV-IR axons were occasionally observed in the white matter underlying the principal sulcus. Electron microscopic analysis revealed that PV-IR somata and dendrites are densely innervated by nonimmunoreactive terminals forming asymmetric (Gray type I) synapses as well as by fewer terminals forming symmetric (Gray type II) synapses. The majority of terminals forming symmetric synapses with PV-IR post-synaptic structures were not immunolabeled; however, some of these boutons did contain PV-immunoreactivity. PV-IR boutons exclusively form symmetric synapses and heavily innervate layer II/III pyramidal cells. PV-IR axon cartridges formed numerous axo-axonic synapses with the axon initial segments of pyramidal cells 15-20 microns beneath the axon hillock and also terminated on large axonal spines of the initial segment. Furthermore, we failed to observe a mixture of PV-immunoreactive and non-immunoreactive boutons composing a single axon cartridge. Pyramidal cell somata and proximal dendrites were also heavily innervated by PV-IR boutons forming symmetric synapses, again, consistent with basket cell innervation. In addition, PV-IR axon terminals frequently formed symmetric synapses with dendritic shafts and spines of unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

The anatomy of dopamine in monkey and human prefrontal cortex.

This chapter reviews recent evidence establishing the comparable organization of dopamine afferents and dopaminergic receptors in the human and monkey prefrontal cortex. Light microscopy using a dopamine-specific antibody reveals that the dopamine innervation in the human prefrontal cortex exhibits a distinct bilaminar distribution with dense bands of fibers in the upper and deeper strata of the cortex, closely resembling the patterning of dopamine fibers in the monkey prefrontal cortex. Also, EM-immunohistochemistry has now revealed identical synaptic complexes both in human and monkey. In both species, dopamine axons from symmetric synapses predominantly on the spines of pyramidal cells. In many cases, the same spine is apposed by an asymmetric, putatively excitatory synapse. Finally, both in human and monkey prefrontal cortex, the dopamine D1-specific ligand, 3H-SCH23390, and the D2-specific ligand, H3-raclopride, label binding sites in laminar positions which match the location of the densest dopamine innervation. These results indicate that the organization of the cortical dopamine system is essentially the same in macaque monkey and human and that the nonhuman primate is a suitable animal model for analysis of dopamine function in prefrontal cortex.

Afferent Pathways↗
PubMed1992

The prefrontal cortex and internally generated motor acts.

The neuroanatomical and neurophysiological data that have been obtained from experimental primates are converging on a framework for understanding the prefrontal influence on motor output. The framework isolates internally memory-based functions from externally guided sensory-based functions, identifies the internally-based functions with prefrontal circuits, the sensory-based functions with premotor circuits, and integrates the specializations of prefrontal, premotor and subcortical structures in the control of motor acts.

Animals↗
PubMed1991

Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans.

Aging↗
PubMed1991

Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.

A remarkable diversity of neurotransmitter receptors develops concurrently in disparate areas of the primate cerebral cortex. The density of dopaminergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors (where GABA is gamma-aminobutyric acid) in rhesus monkey reaches a maximum level between 2 and 4 months of age and then declines gradually to adult levels in all layers of sensory, motor, and association regions. The synchronized development of neurotransmitter receptors in diverse layers and regions of the neocortex occurs pari passu with synaptogenesis, demonstrating unusual coordination of biochemical and structural maturation and supporting the hypothesis that the entire cerebral cortex matures as an integrated network, rather than as a system-by-system cascade.

Aging↗
PubMed1991

Myelo- and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca.

As the first part of a comparative investigation of primate frontal cortex, we compared the frontal architectonic organization of Galago, a small-brained, strepsirhine (or "prosimian") primate, to that of an anthropoid primate, Macaca, by using myelin- and Nissl-stained material. We were able to distinguish many more areas in both taxa than have been recognized in most previous studies of the primate frontal lobe. In particular, we were able to subdivide many of the areas shown in the commonly cited architectonic map of Walker (J. Comp. Neurol. 73:59-86, 1940). Delineation of areas was greatly facilitated by the use of the Gallyas technique for staining myelin. The areal organization of much of frontal cortex (specifically, the premotor, orbital, and medial regions) appears to be very similar in Galago and Macaca. In these regions, we were able to recognize the same complement of areas in both taxa, with few exceptions. In the granular frontal cortex (GFC), by contrast, we were able to distinguish about twice as many areas in Macaca as in Galago. For most of the GFC areas of Galago, there are architectonically similar areas in Macaca; the areas shared by both taxa correspond mainly to the arcuate and superior areas of Macaca (i.e., the region encompassed by Walker's areas 45, 8A, and 8B). However, there are many additional, more rostral, areas in Macaca for which there are no obvious homologues in Galago. In particular, Galago lacks cortex resembling the distinctive, lightly myelinated cortex of the Macaca principal sulcus (Walker's area 46 and its subdivisions). Our results are difficult to reconcile with the view that frontal lobe organization varies little across taxa. Rather, they suggest that granular frontal cortex underwent considerable change during primate evolution, including the addition of new areas in anthropoids.

Animals↗
PubMed1991

Architectonics of the parietal and temporal association cortex in the strepsirhine primate Galago compared to the anthropoid primate Macaca.

A number of higher order association areas have been described in the parietal and temporal cortex of large-brained anthropoid primates such as Macaca. However, little is known about the evolution of these areas, and the existence of homologous areas has not yet been clearly demonstrated in other mammalian groups. We addressed this issue by comparing the myelo- and cytoarchitecture of posterior association cortex in the anthropoid Macaca to that of the small-brained, strepsirhine ("prosimian") primate Galago. Our results suggest that Galago possesses many, if not most, of the areas present in Macaca. We were able to identify regions in Galago which resemble Macaca posterior parietal area 7, superior temporal polysensory cortex (ST), inferotemporal visual cortex (IT), the temporoparietal auditory area (Tpt), and posterior parahippocampal cortex (areas TH and TF). Area 7, ST, and IT can each be subdivided further in Macaca, and for most of these subdivisions we were able to identify counterparts in Galago. However, we could not distinguish as many divisions of ST cortex in Galago as in Macaca, and it is possible that new areas arose in this region during anthropoid evolution. There also appear to be general differences in architectonic organization between these animals, with Macaca exhibiting greater development of pyramidal layer IIIc and of the internal granular layer (IV) across much of the parieto-temporal cortex. These findings suggest that many, although possibly not all, of the parietal and temporal association areas present in the modern anthropoid Macaca evolved early in primate history, prior to the divergence of the lineages leading to strepsirhines and anthropoids.

Animals↗