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)     

子宫内膜异位症猕猴动物模型的建立

目的构建子宫内膜异位症(EM)猕猴动物模型。方法选择5只健康、月经规律的雌性猕猴(4只实验猴、1只对照猴),在月经第8~15天,雌激素高峰的第3~5天,手术将猕猴的子宫内膜种植到盆腔子宫腔以外的部位,对照猕猴用大网膜取代内膜种植。在术后第2、4个月动物月经周期的第8~15天开腹或腹腔镜探查。结果术后第2个月探查,4只实验猴中,3只异位内膜种植存活,其中2只形成异位囊肿。术后第4个月,对2只已形成EM的猕猴行腹腔镜再次探查,其盆腔粘连,异位内膜生长情况与术后第2个月基本相似;3只形成EM的猕猴精神状态、饮食、体质量增长情况均较对照猕猴差,2只发生肠套叠死亡。结论本研究根据种植学说原理成功地构建了子宫内膜异位症猕猴动物模型,但猕猴的个体差异是模型是否成功的一个关键因素,因而认为遗传因素是子宫内膜异位症发病中的另一重要机制,子宫内膜异位生长对机体的整体机能有较为明显的影响。     

Neurons in the Primate Superior Colliculus are Active Before and During Arm Movements to Visual Targets

The activity of single neurons in the superior colliculus was recorded while a rhesus monkey made arm movements to visual targets located on a screen in front of him. It was found that the activity of a subpopulation of cells was clearly related to these arm movements. The neurons began to discharge either with the onset of the movement, during the movement period, or well before the onset of electromyogram (EMG) activity and movement, and could be active for the entire duration of EMG activity. While the discharge pattern of some of these'reach'neurons was not different for movements to different target positions, other cells showed graded changes in activity depending on the direction of movement. The peak discharge rate could rise to > 100 impulses/s. Some units received somatosensory input; other reach cells exhibited a visual response and/or presaccadic activity. It is likely that the primate superior colliculus is not only involved in the initiation and control of orientating movements of the eyes but also in reaching movements of the arms.     

Gamma delta T cells in rhesus monkeys and their response to simian immunodeficiency virus (SIV) infection.

The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.     

Interaction of sensory and cognitive processes during visual recognition: The role of the associative areas of the cerebral cortex

The first part of the present study used a model of Alzheimers disease in two groups of animals (three monkeys in each), given injections of neurotoxins (monkeys of group I) and physiological saline (monkeys of group II). Before injections, all monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids and geometrical figures of different colors and with different spatial relationships between objects) and to perform spatial selection. The dynamics of impairments in the characteristics of working memory were identified using delayed differentiation tasks in monkeys of both groups before injections and every two months after injections. Quantitative measures of impairments were made using the entropy of visual recognition, which characterizes uncertainty in decision-taking. The development of Alzheimers disease in rhesus macaques was characterized by a deficit of working memory, resulting from lesions to the two component processes of memory. Impairments of the first of these in monkeys of group I were manifest as a significant increase in entropy, which is associated with correct decision-taking. The magnitude of the increase depended on the type of visual information. Impairments of the second component were characterized by increases in entropy associated with refusals to take decisions and were independent of the delay duration and the type of visual information. Monkeys given injections of physiological saline showed no significant changes in these characteristics. The features of working memory were also studied in the second part of the investigation, using four groups of Rhesus macaques: intact, those with bilateral extirpation of the sulcus principalis or field 7 or both: degradation again identified two components. Entropy associated with this was increased significantly for most of the stimuli tested on monkeys of all extirpation groups as compared with intact animals. Significant differences were found in these characteristics for a number of stimuli, which depended on the location of the structures removed. The characteristics of impairments of the components of working memory resulting in the development of Alzheimers disease showed that the cholinergic mechanisms responsible for sensory processing differ from those involved in decision-taking. The structural-functional organization of the interaction of sensory and cognitive processes controlled by the motivation and attention systems is discussed, as is the role of the associative areas of the cortex.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 10, pp. 1226–1239, October, 2003.     

The functional organization of the intraparietal sulcus in humans and monkeys

In macaque monkeys, the posterior parietal cortex (PPC) is concerned with the integration of multimodal information for constructing a spatial representation of the external world (in relation to the macaque's body or parts thereof), and planning and executing object-centred movements. The areas within the intraparietal sulcus (IPS), in particular, serve as interfaces between the perceptive and motor systems for controlling arm and eye movements in space. We review here the latest evidence for the existence of the IPS areas AIP (anterior intraparietal area), VIP (ventral intraparietal area), MIP (medial intraparietal area), LIP (lateral intraparietal area) and CIP (caudal intraparietal area) in macaques, and discuss putative human equivalents as assessed with functional magnetic resonance imaging. The data suggest that anterior parts of the IPS comprising areas AIP and VIP are relatively well preserved across species. By contrast, posterior areas such as area LIP and CIP have been found more medially in humans, possibly reflecting differences in the evolution of the dorsal visual stream and the inferior parietal lobule. Despite interspecies differences in the precise functional anatomy of the IPS areas, the functional relevance of this sulcus for visuomotor tasks comprising target selections for arm and eye movements, object manipulation and visuospatial attention is similar in humans and macaques, as is also suggested by studies of neurological deficits (apraxia, neglect, Bálint's syndrome) resulting from lesions to this region.     

Long-term effects of infant rearing condition on the acquisition of dominance rank in juvenile and adult rhesus macaques (Macaca mulatta)

We examined the effects of early rearing experience on the development of dominance status in 53 juvenile (age 3) and then in 38 adult (ages 5-8) rhesus macaques. Based on previous research investigating the behavioral outcomes of nursery-rearing, we predicted that mother-reared (MR) monkeys would outrank peer-only reared (PR) monkeys, which would in turn outrank surrogate/peer-reared (SPR) subjects. Juvenile MR and PR subjects did not differ in ranks, but monkeys from both rearing backgrounds outranked SPR cage-mates at age 3. Independent of rearing condition, high-ranking juveniles gained the most weight between ages 1-3, suggesting that low status may be associated with decreases in early weight gain. Adult MR subjects outranked both PR and SPR subjects, with PR animals occupying intermediate ranks. These results indicate that impoverished early experiences, such as adult absence and limited social interaction, are useful predictors of future social success in rhesus macaques.     

An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS.     

中国恒河猴(Macaca mulatta)外周血CD4+CD25+T淋巴细胞的研究

目的:研究中国恒河猴外周血中CD4 CD25 T淋巴细胞亚群及其分布频率。方法:利用流式细胞术对50只中国恒河猴外周血CD4 CD25 T淋巴细胞进行了分析。结果:发现所有被检测的恒河猴个体中均存在明显的CD4 CD25 T淋巴细胞亚群;CD4 CD25 T淋巴细胞大约占CD4 T淋巴细胞的9.1%(变化范围为2.6%～18.1%);其中CD4 CD25highT淋巴细胞约占2.5%(0.3%～5.5%)。对不同年龄和性别个体中CD4 CD25 T淋巴细胞频率的初步分析未发现统计学上有年龄或性别差异。结论:中国恒河猴可用于与CD4 CD25 T细胞相关的人类疾病的研究中。     

The entorhinal cortex of the monkey: I. Cytoarchitectonic organization

As an essential preliminary to a series of experimental studies of the afferent and efferent connections of the monkey entorhinal cortex, we have carried out a detailed analysis of its cytoarchitectonic organization. Primarily on the basis of features observed in Nissl- and fiber-stained preparations, supplemented with Golgi-stained material and preparations stained for heavy metals by Timm's method and histochemically for acetylcholinesterase, the entorhinal cortex has been divided into seven fields that are named according to their rostrocaudal and mediolateral positions except for one rostrally located field that is named for the prominent input that it receives from the olfactory bulb. At rostral levels, the entorhinal cortex is marked by a number of morphological inhomogeneities. The neurons tend to be organized in patches that are surrounded by large, thick, radially oriented bundles of fibers. At caudal levels, the entorhinal cortex has a more distinctly laminated appearance, reminiscent of that in the neocortex, and most of the neurons and fiber fascicles are arranged in discrete radial columns. The cortical region adjoining the entorhinal cortex laterally, which is commonly known as the "perirhinal cortex," is in fact composed of two separate fields corresponding to areas 35 and 36 of Brodmann. Area 35 occupies the fundus and part of the lateral aspect of the rhinal sulcus. Area 36 extends from the lateral bank of the rhinal sulcus into the inferior temporal gyrus, where it borders fields TA and TE rostrally, and field TF of the parahippocampal gyrus caudally. The surface extents of each of the entorhinal fields have been determined by making "unfolded" two-dimensional maps of the region and measuring the areas with a computerized digitizing system.