Biomedical subjects

P S Goldman-Rakic

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

At least 163 records · Page 9Linked to original sources

PubMed1988

Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior.

Common efferent projections of the dorsolateral prefrontal cortex and posterior parietal cortex were examined in 3 rhesus monkeys by placing injections of tritiated amino acids and HRP in frontal and parietal cortices, respectively, of the same hemisphere. Terminal labeling originating from both frontal and parietal injection sites was found to be in apposition in 15 ipsilateral cortical areas: the supplementary motor cortex, the dorsal premotor cortex, the ventral premotor cortex, the anterior arcuate cortex (including the frontal eye fields), the orbitofrontal cortex, the anterior and posterior cingulate cortices, the frontoparietal operculum, the insular cortex, the medial parietal cortex, the superior temporal cortex, the parahippocampal gyrus, the presubiculum, the caudomedial lobule, and the medial prestriate cortex. Convergent terminal labeling was observed in the contralateral hemisphere as well, most prominently in the principal sulcal cortex, the superior arcuate cortex, and the superior temporal cortex. In certain common target areas, as for example the cingulate cortices, frontal and parietal efferents terminate in an array of interdigitating columns, an arrangement much like that observed for callosal and associational projections to the principal sulcus (Goldman-Rakic and Schwartz, 1982). In other areas, frontal and parietal terminals exhibit a laminar complementarity: in the depths of the superior temporal sulcus, prefrontal terminals are densely distributed within laminae I, III, and V, whereas parietal terminals occupy mainly laminae IV and VI directly below the prefrontal bands. Subcortical structures also receive apposing or overlapping projections from both prefrontal and parietal cortices. The dorsolateral prefrontal and posterior parietal cortices project to adjacent, longitudinal domains of the neostriatum, as has been described previously (Selemon and Goldman-Rakic, 1985); these projections are also found in close apposition in the claustrum, the amygdala, the caudomedial lobule, and throughout the anterior medial, medial dorsal, lateral dorsal, and medial pulvinar nuclei of the thalamus. In the brain stem, both areas of association cortex project to the intermediate layers of the superior colliculus and to the midline reticular formation of the pons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Quantitative autoradiography of major neurotransmitter receptors in the monkey striate and extrastriate cortex.

In vitro autoradiography was used to determine the binding properties and distribution of 9 major neurotransmitter receptors and their subtypes in the striate (area 17 of Brodmann) and extrastriate (areas 18 and 19) cortex of 1 infant and 3 adult rhesus monkeys. Differences in total labeling and nonspecific labeling, as well as Kd and Bmax values, were determined for all cortical layers and sublayers in both cytoarchitectonic areas by Scatchard analysis of autoradiograms. Area 17 differed from area 18 in the laminar pattern and density of virtually every ligand examined, i.e., 3H-clonidine, 3H-prazosin, 125I-iodopindolol, 3H-quinuclidinyl benzilate, 3H-5-hydroxytryptamine, 3H-ketanserin, 3H-muscimol, 3H-flunitrazepam, and 3H-spiperone. Kd and Bmax values for each ligand were remarkably consistent across the 3 adult monkeys analyzed quantitatively. Particularly dramatic contrasts were observed with clonidine, 5-hydroxytryptamine, and ketanserin, which have high affinity for alpha 2-adrenergic, 5-HT1-, and 5-HT2-receptors, respectively. The differences in distribution of these ligands, especially clonidine and 5-hydroxytryptamine, correlated well with specific laminae and hence exhibited distinctly different patterns in areas 17 and 18. Other ligands, such as flunitrazepam and quinuclidinyl benzilate that bind to GABAergic and cholinergic receptors, were visually less discriminating both among layers and between regions. However, layer for layer, the Bmax values for quinuclidinyl benzilate were higher in area 17 than 18, indicating the subtle differences between areas may be revealed only by quantitative measures. Some ligands were particularly dense in layer I (iodopindolol in areas 17 and 18; 5-hydroxytryptamine in area 18), and others subdivided cortical layers that are otherwise cytoarchitectonically uniform (e.g., flunitrazepam and clonidine in layer VI of area 17), indicating that areal differences in ligand binding are not a simple read-out of cell-packing density but most likely reflect a genuine difference related to the neurotransmitters of intrinsic and extrinsic afferents in each area. The presence of binding sites in every layer of both areas for all ligands examined indicates that their distribution across laminae is quantitative and not all-or-none. No layer contained less than 50% of binding sites present in any other layer. These findings reveal that visual cortical areas differ in density and lamination of neurotransmitter receptors and presumably in their sensitivity to circulating levels of endogenous neurotransmitters and pharmacologically active compounds.

Animals↗

PubMed1988

The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes.

The present study attempted to identify an alpha-2 agonist that could improve working memory in aged nonhuman primates without the marked hypotensive and sedative side effects produced by clonidine. Toward this end, the hypotensive, sedative, and memory-altering properties of the alpha-2 adrenergic agonists, B-HT920 and guanfacine, were compared with clonidine's effects in 9 aged rhesus monkeys. Memory capacity was assessed by a variable delay, spatial delayed response paradigm that requires the animal to remember information over short temporal intervals and to update this information on every trial. B-HT920 was found to produce a dose-response profile qualitatively similar to, but weaker than, clonidine: low doses impaired memory and began to lower blood pressure and produce sedation, while high doses improved memory. In contrast, guanfacine produced a dose-response profile opposite to that seen with clonidine: low doses improved memory without inducing hypotension or sedation, while the memory-impairing, hypotensive, and sedating properties of the drug were observed at higher doses. The potency of the 3 agonists to lower blood pressure was clonidine = B-HT920 greater than guanfacine; sedation was affected in the order clonidine greater than B-HT920 greater than guanfacine; for memory impairment, as measured by performance on the delayed response task, the rank order potency was clonidine greater than B-HT920 greater than guanfacine, while for memory improvement it was guanfacine greater than clonidine greater than B-HT920. These differences in rank order potency are consistent with the recent proposal of alpha-2 receptor subtypes, a rauwolscine-sensitive site (Rs) that binds clonidine greater than B-HT920 greater than guanfacine and a rauwolscine-insensitive site (Ri) that binds guanfacine greater than clonidine greater than B-HT920 (Boyajian and Leslie, 1987). The data suggest that the hypotensive, sedating, and memory-impairing effects of alpha-2 agonists may be due to actions at one subtype of receptor (Rs), while the memory-enhancing effects of these drugs may result from actions at another alpha-2 receptor subtype, the Ri site. The ability of low doses of guanfacine to improve memory without inducing hypotension or sedation indicates that this agonist may be an excellent candidate for treating memory disorders in man.

Adrenergic alpha-Agonists↗

PubMed1988

Activation of the hippocampus and dentate gyrus by working-memory: a 2-deoxyglucose study of behaving rhesus monkeys.

The 2-deoxyglucose method was used to examine metabolic activity in the hippocampus, dentate gyrus, and amygdala of rhesus monkeys performing working-memory and control tasks. A working-memory group was tested on 1 of 3 tasks requiring trial-by-trial updating of information: delayed spatial response, delayed spatial alternation, or delayed object alternation. A control group was tested either on an associative memory problem, visual pattern discrimination, or a sensory-motor task that did not have an explicit mnemonic component. Local cerebral glucose utilization (LCGU) in specific layers of the dentate gyrus and the CA1 and CA3 sectors of the hippocampus, as well as in 7 distinct nuclei of the amygdala, was measured and compared across groups. Metabolic rate in specific layers of the dentate gyrus and the CA3 and CA1 fields of the hippocampus was enhanced in the working-memory compared with the control group: LCGU was between 18 and 24% higher in the granule cell and molecular layers of the dentate gyrus and in the molecular and radiatum layers of CA1 and CA3 in the hippocampus. In contrast, no significant group differences in LCGU were found for any of the 7 amygdaloid nuclei examined: the lateral, lateral basal, medial basal, accessory basal, cortical, central, and medial nuclei. These results are consistent with previous evidence showing that lesions of the hippocampus affect memory selectively, producing deficits on some memory problems while sparing others. Our findings further suggest that working-memory may be a common denominator among those tasks that are sensitive to hippocampal damage in monkeys. The contribution of the amygdala to performance on memory tasks, on the other hand, appears to be independent of the specific type of memory process that is engaged.

Amygdala↗

PubMed1988

Periodicity of GABA-containing cells in primate prefrontal cortex.

The tangential distribution of GABA-containing cells was examined in the principal sulcus of the frontal lobe in 12 macaque monkeys. Following immunostaining with GABA antisera all immunoreactive cells were charted and their distribution analyzed with both statistical and spectral density methods. In addition, a gapless series of sections was used to generate a 2-dimensional reconstruction of cell disposition in the tangential plane parallel to the pia. Our findings indicate that the GABA cells are not distributed uniformly across the cortex, as is commonly believed, but that their density is characterized by 2 independent sinusoidal fluctuations: a high-frequency component with a period ranging from 150 to 250 micron superimposed upon a lower-frequency component with a period of 1000-1275 micron. The half-cycle of the low-frequency component (roughly 625 micron) is very similar to the dimensions of afferent and efferent columns in the principal sulcus, while the half-cycle of the higher-frequency component (approximately 125 micron) is closer in size to that of the functionally defined columns of neurons found in regions of sensory cortex that share common physiological properties. To our knowledge, these findings are the first indication that inhibitory local circuit neurons are not uniformly or randomly distributed, but exhibit periodicities that may be related to the columnar, functional and architectural organization of the cortex.

Animals↗

PubMed1987

Regional distribution of cholecystokinin receptors in primate cerebral cortex determined by in vitro receptor autoradiography.

Cholecystokinin (CCK) is a putative peptide neurotransmitter present in high concentration in the cerebral cortex. By using techniques of in vitro receptor autoradiography, CCK binding sites in primate cortex were labeled with 125I-Bolton-Hunter-labeled CCK-33 (the 33-amino-acid C-terminal peptide) and 3H-CCK-8 (the C-terminal octapeptide). Biochemical studies performed on homogenized and slide-mounted tissue sections showed that the two ligands labeled a high-affinity, apparently single, saturable site. Autoradiography revealed that binding sites labeled by both ligands were anatomically indistinguishable and were distributed in two basic patterns. A faint and diffuse label characterized portions of medial prefrontal cortex, premotor and motor cortices, the superior parietal lobule, and the temporal pole. In other cortical areas the pattern of binding was layer-specific; i.e., binding sites were concentrated within particular cortical layers and were superimposed upon the background of diffuse label. Layer-specific label was found in the prefrontal cortex, anterior and posterior cingulate gyrus, somatosensory cortex, inferior parietal lobule, retrosplenial cortex, insula, temporal lobe cortices, and in the primary visual and adjacent visual association cortices. The areal and laminar localization of layer-specific CCK binding sites consistently coincided with the cortical projections of thalamic nuclei. In prefrontal cortex, CCK binding sites were present in layers III and IV, precisely paralleling the terminal fields of thalamocortical projections from the mediodorsal and medial pulvinar nucleus of the thalamus. In somatosensory cortex, the pattern of CCK binding in layer IV coincided with thalamic inputs arising from the ventrobasal complex, while in the posterior cingulate gyrus, insular cortex, and retrosplenial cortex, layer IV and lower III binding mirrored the laminar distribution of cortical afferents of the medial pulvinar. CCK binding in layers IVa, IVc alpha, IVc beta, and VI of primary visual cortex corresponded to the terminal field disposition of lateral geniculate neurons, whereas in adjacent visual association cortex, binding in layers III, IV, and VI faithfully followed the cortical distribution of projections from the inferior and lateral divisions of the pulvinar nucleus of the thalamus. We interpret the diffusely labeled binding sites in primate cortex as being associated with the intrinsic system of CCK-containing interneurons that are distributed throughout all layers and areas of the cortex. The stratified binding sites, however, appear to be associated with specific extrinsic peptidergic projections.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

Crossed corticothalamic and thalamocortical connections of macaque prefrontal cortex.

We have conducted a systematic comparison of the ipsilateral (uncrossed) and contralateral (crossed) thalamic connections of prefrontal cortex in macaque monkeys, using cortical implants of horseradish peroxidase pellets and tetramethyl benzidine histochemistry to demonstrate anterograde and retrograde thalamic labeling. Contrary to the prevailing belief that thalamocortical projections are entirely uncrossed, our findings indicate that a modest crossed projection to prefrontal cortex arises from the mesial thalamus, principally the anteromedial and midline nuclei. Also, while confirming that corticothalamic projections are bilateral, we found that the pattern of crossed projections differs from that of uncrossed projections. Projections to mesial thalamic nuclei, specifically to the anteromedial nucleus, the midline nuclei, and the magnocellular part of the mediodorsal nucleus are bilateral, the contralateral projection being nearly as dense as the ipsilateral projection. Projections to the parvicellular part of the mediodorsal and ventral anterior nuclei are also bilateral, but the contralateral projection is much weaker than the ipsilateral projection. Prefrontal projections to the reticular nucleus, medial pulvinar, suprageniculate nucleus, and limitans nucleus appear to be exclusively ipsilateral. These results indicate that prefrontal cortex has prominent bilateral and reciprocal connections with the nuclei of the mesial thalamic region. As this region of the diencephalon has been implicated by anatomical and behavioral studies in memory functions, our findings suggest that prefrontal cortex, through its connections with this region, may be involved in the bilateral integration of mnemonic systems.

Animals↗

PubMed1987

Motor control function of the prefrontal cortex.

The prefrontal granular cortex, with the premotor and motor areas, forms the frontal lobe. The three areas are allied by their proximity to one another and by their role in motor control. Of these three major subdivisions, the role of prefrontal cortex has been the most obscure. However, recent anatomical studies have elucidated the circuit basis for motor regulatory functions of the principal sulcus (Brodmann's area 9; Walker's area 46). In addition to well known and well worked out prominent connections with subcortical structures, e.g. the basal ganglia and deep layers of the superior colliculus, this area of prefrontal cortex is reciprocally connected to portions of the supplementary motor and premotor fields that are but one synapse removed from primary motor cortex. The principal sulcal cortex is additionally interconnected with the primary somatosensory area and the somatosensory association areas, in the frontoparietal operculum, with area PF of von Bonin and Bailey in the posterior parietal cortex, and with parts of the 'motor' thalamus. Recent behavioural and electrophysiological studies in monkeys (Macaca mulatta) demonstrate that the principal sulcus can influence delayed-responding, whether the response is a hand or an eye movement. The anatomical and functional evidence supports the thesis that prefrontal cortex has access to and can direct the output of several motor centres.

Animals↗

PubMed1987

A sequential double-label 14C- and 3H-2-DG technique: validation by double-dissociation of functional states.

We investigated a double-label 2-DG protocol and method of analysis in which sequential injections of 3H- and 14C-2-DG were used to map brain metabolism during two distinct experimental treatments in the same animal. In initial studies, brain sections from rats given only 3H-2-DG or only 14C-2-DG were exposed on Ultrofilm and on X-ray film with an interposed sheet of mylar (X-ray/mylar). These studies were needed to determine whether, at the 50:1 3H:14C dose ratio used, 3H-2-DG uptake would be revealed only in Ultrofilm images and 14C-2-DG uptake only in X-ray/mylar images. We found that X-ray/mylar images indeed showed only 14C-2-DG uptake as 3H emissions were blocked by the protective coating of the film and the mylar. By contrast, Ultrofilm autoradiograms showed the 2-DG uptake pattern for both the 14C-2-DG and 3H-2-DG cases. We then examined autoradiograms from double-label cases in which 14C-2-DG and 3H-2-DG were sequentially given using a 100:1 3H:14C dose ratio, with a different treatment following each injection. As predicted from the single-label cases, activity in the X-ray/mylar images corresponded to the treatment that followed the 14C-2-DG injection, while the Ultrofilm images reflected both treatments and thus were not veridical representations of 3H label. This paper provides a solution to the contamination of Ultrofilm by 14C label in that we devised a subtraction algorithm using a computerized imaging system which removes the contaminating 14C from the Ultrofilm image, leaving a 'Difference' image of 3H-2-DG uptake. Difference images revealed activity consistent with the treatment that followed the 3H-2-DG injection. Thus, the X-ray/mylar and difference images separately indexed metabolic activity for two different functional states in the same subject. By allowing a subject to serve as its own control, this double-label method greatly increases the applicability and power of the 2-DG method.

Algorithms↗

PubMed1987

Circuitry of the frontal association cortex and its relevance to dementia.

The prefrontal cortex reaches its peak size and complexity in the human brain where it occupies more than a quarter of the cerebral cortical surface. This paper reviews studies on that portion of the prefrontal cortex that is buried in and around the principal sulcus of macaque monkeys and corresponds to Brodmann's area 46 in man. Neuropsychological research as well as neurophysiology and 2-deoxyglucose metabolic mapping indicate that the principal sulcus is essential for regulation of motor behavior by internalized representations of visuo-spatial events. Conversely, the prefrontal cortex is unnecessary for behavior regulated by external stimuli, as is the case with many associative learning and recognition memory processes. Research over the past decade suggests that the principal sulcus accomplishes its regulatory functions by its interconnections with (1) the posterior parietal cortex which provides it with access to visuo-spatial data, (2) the parahippocampal gyrus and subiculum which allows information to be held 'on line' and deposited in long-term storage, and (3) motor centers such as the basal ganglia, deep layers of the superior colliculus and several premotor areas that control head, eye and hand movements. In addition, modulatory influences on prefrontal functions are exerted by (4) dopamine-, norepinephrine- and serotonin-containing fiber systems that originate in the brain stem and innervate the prefrontal cortex in a selective manner. Comparison between syndromes present in patients with a variety of diagnoses and human and nonhuman subjects with prefrontal injuries provides suggestive evidence that prefrontal dysfunction may underly the disordered thinking and abnormal social and affective responses found in many of these diseases. Accordingly, knowledge of the neural mechanisms underlying cognitive processing in nonhuman primates should be helpful in the analysis of the 'neurology' of many neurological and psychiatric illnesses.

Animals↗

PubMed1987

Noradrenergic mechanisms in age-related cognitive decline.

The alpha-2 agonist, clonidine, improved spatial working memory performance in 13/13 aged rhesus monkeys with documented memory impairments. The clonidine response was blocked by alpha-2, but not alpha-1 antagonists, and appeared to result from actions at postsynaptic alpha-2 receptors in that area of cortex most critical for spatial working memory, the principal sulcal cortex. The data indicate that noradrenergic mechanisms play an important role in the functioning of the frontal association cortex, and support the rationale for giving alpha-2 agonists to restore this function in Alzheimer's patients with profound norepinephrine loss.

Aging↗

PubMed1987

Development of cortical circuitry and cognitive function.

Recent functional and anatomical studies in nonhuman primates have elucidated the basic neural circuitry underlying delayed-response function in adult nonhuman primates. Thus circuitry includes connections of the principal sulcus with other areas of parietal association and limbic cortex and projections to the caudate nucleus, superior colliculus, and other premotor centers. Anatomical tracing in primate fetuses and in monkeys at various stages of postnatal development indicates that these various classes of cortical connections begin to form by the second trimester of pregnancy. Electromicroscopic studies of the principal sulcus and other areas of cerebral cortex show that the number and density of synapses in the cortex increase rapidly, reaching and maintaining higher than normal adult values between 2 and 4 months postnatally, before slowly declining over a period of years to stable adult levels. The capacity to perform delayed-response and/or AB at short delays emerges around 4 months of age, coinciding with the end of the period of highest synaptic density in the principal sulcus. These findings suggest that a critical mass of cortical synapses is important for the emergence of this cognitive function, and that fully mature capacity may depend upon the elimination of excess synapses that occurs during adolescence and young adulthood. Knowledge of the neural basis of normal cognitive development may prove useful both to social and educational purposes as well as to understanding developmental disorders of cognition.

Animals↗

PubMed1986

Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex.

Synapses develop concurrently and at identical rates in different layers of the visual, somatosensory, motor, and prefrontal areas of the primate cerebral cortex. This isochronic course of synaptogenesis in anatomically and functionally diverse regions indicates that the entire cerebral cortex develops as a whole and that the establishment of cell-to-cell communication in this structure may be orchestrated by a single genetic or humoral signal. This is in contrast to the traditional view of hierarchical development of the cortical regions and provides new insight into the maturation of cortical functions.

Animals↗

PubMed1986

Estrogen formation and binding in the cerebral cortex of the developing rhesus monkey.

These studies were undertaken to determine whether estrogen receptors and the microsomal enzyme system called the aromatase complex, which is responsible for conversion of androgen to estrogen, are present in the brain of the rhesus monkey during perinatal life. Four monkeys (three females--one fetus removed on day 153 of gestation and two infants, 5 and 6 days postnatal--and 1 male, 2 days postnatal) were studied. Cytosol estrogen receptors were detected in all brain regions examined. The apparent equilibrium dissociations constants for reaction of these sites with [3H]moxestrol were similar to those for uterine and pituitary cytosol estrogen receptors (0.3-1.1 nM). Within the brain, highest levels of binding were observed in the hypothalamus-preoptic area, with fairly even, lower concentrations throughout the cortical structures. Aromatase complex activity was detected in the majority of the tissue specimens. The highest levels of estrogen formation were observed in the hypothalamus. However, the amygdala, the hippocampus, and several of the cortex samples also contained measurable aromatase complex activity. Among the cortical samples, the highest levels of aromatase complex activity were found in regions of the association cortex (the dorsolateral-prefrontal, orbital-prefrontal, anterior cingulate, and parietal cortices). The lowest levels of aromatase activity were found in the somatosensory and motor cortices of the postnatal animals. These results suggest that locally-formed estrogen may be involved in the effects of circulating androgens on the developing primate neocortex.

Animals↗

PubMed1985

The primate mediodorsal (MD) nucleus and its projection to the frontal lobe.

The frontal lobe projections of the mediodorsal (MD) nucleus of the thalamus were examined in rhesus monkey by transport of retrograde markers injected into one of nine cytoarchitectonic regions (Walker's areas 6, 8A, 9, 10, 11, 12, 13, 46, and Brodmann's area 4) located in the rostral third of the cerebrum. Each area of prefrontal, premotor, or motor cortex injected was found to receive a topographically unique thalamic input from clusters of cells in specific subdivisions within MD. All of the prefrontal areas examined also receive topographically organized inputs from other thalamic nuclei including, most prominently, the ventral anterior (VA) and medial pulvinar nuclei. Conversely, and in agreement with previous findings, MD projects to areas of the frontal lobe beyond the traditional borders of prefrontal cortex, such as the anterior cingulate and supplementary motor cortex. The topography of thalamocortical neurons revealed in coronal sections through VA, MD, and pulvinar is circumferential. In the medial part of MD, for example, thalamocortical neurons shift from a dorsal to a ventral position for cortical targets lying medial to lateral along the ventral surface of the lobe; neurons in the lateral MD move from a ventral to a dorsal position, for cortical areas situated lateral to medial on the convexity of the hemisphere. The aggregate evidence for topographic specificity is supported further by experiments in which different fluorescent dyes were placed in multiple areas of the frontal lobe in each of three cases. The results show that very few, if any, thalamic neurons project to more than one area of cortex. The widespread cortical targets of MD neurons together with evidence for multiple thalamic inputs to prefrontal areas support a revision of the classical hodological definition of prefrontal cortex as the exclusive cortical recipient of MD projections. Rather, the prefrontal cortex is defined by multiple specific relationships with the thalamus.

Animals↗

PubMed1985

Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates.

This study provides evidence that the alpha 2-adrenergic receptor agonist clonidine ameliorates the cognitive deficits exhibited by aged nonhuman primates through drug actions at alpha 2 receptors. Furthermore, pharmacological profiles in animals with lesions restricted to the dorsolateral prefrontal cortex indicate that this area may be the site of action for some of clonidine's beneficial effects. These results demonstrate that alpha-adrenergic systems contribute to cognitive function and suggest a new strategy for treating memory disorders in aged humans.

Aging↗

PubMed1985

Organization of the nigrothalamocortical system in the rhesus monkey.

The nigrothalamocortical connections and their topography were analyzed by autoradiography and double or triple retrograde labeling with the fluorescent dyes Fast Blue, Diamidino Yellow, and Propidium Iodide. Injections of tritiated leucine into different parts of the substantia nigra (SN) revealed that the medial SN projects to the medial magnocellular subdivisions of the ventral anterior (VAmc) and mediodorsal (MDmc) nuclei of the thalamus while the lateral SN projects to the more lateral and more posterior part of the VAmc, and the paralaminar, parvicellular, and densocellular subdivisions of the mediodorsal nucleus (MDmf, MDpc, and MDdc). With the exception of the MDmf, terminal areas observed in the mediodorsal nucleus were in the form of scattered clusters of grains. Analysis of the thalamus in cases with fluorescent dye injections into the lateral orbital gyrus (Walker's area 11), principal sulcus (area 46), anterior bank of the arcuate gyrus (areas 8 and 45), supplementary motor area (area 6), and motor cortex (area 4) revealed topographic organization of the nigrothalamocortical projection system. The parts of the VAmc and MDmc which receive afferents from the medial part of the SN in turn project to the most anterior regions of the frontal lobe including principal sulcus and orbital cortex. The lateral posterior VAmc, MDmf, MDpc, and MDdc, all of which receive afferents from the lateral part of the SN; project to more posterior regions of the frontal lobe including, in addition to the principal sulcus, the frontal eye field and also areas of the premotor cortex. These findings indicate that the SN has preferential targets in the thalamus and cerebral cortex which are segregated from those of the globus pallidus and cerebellum. Whereas the motor cortex is the primary target of cerebellar output (Asanuma et al., '83b), and the premotor cortex is the target of pallidal output (Schell and Strick, '84), the SN output appears to be directed more anteriorally--to the prefrontal cortex.

Animals↗

PubMed1985

Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans.

Thiamine deficiency in the monkey is the animal counterpart of Wernicke's disease in humans. In the present study, thiamine deficiency was induced in 11 monkeys while three monkeys were given paired feedings supplemented by thiamine hydrochloride and three monkeys were maintained on regular chow. The typical clinical symptoms were apathy, inattention to peripheral stimuli, ataxia, ptosis, mydriasis progressing to pupillary areflexia, nystagmus, and ophthalmoparesis progressing to total ophthalmoplegia. With thiamine treatment, recovery was prompt and complete in mild to moderate cases but delayed and incomplete in severe cases. The animals were killed six or more months after discontinuance of the experiments to determine the chronic effects of treated thiamine deficiency. The significant abnormalities in the brain stem were symmetric gliosis and neuronal loss in the inferior colliculi, the regions of the third and sixth nerve nuclei, and the medial vestibular nuclei. White matter was characteristically spared. With the exception of the inferior colliculi, the target sites for neuropathologic changes were the centers for ocular motor control.

Animals↗