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Characterization of the integrity of three-dimensional trabecular bone microstructure by connectivity and shape analysis using high-resolution magnetic resonance imaging in vivo.

Bone mineral density and bone structure are the main determinants of bone strength in osteoporosis. In this study we used high-resolution magnetic resonance imaging to visualize the bone microstructure in the finger phalanges in vivo and to assess the topological three-dimensional connectivity of the trabecular network and the shape of the trabeculae as measures of bone quality. We visualized the phalanges of young and elderly healthy volunteers in vivo with a spatial resolution of 152 microm x 152 microm x 280 microm. Image processing software to quantify three measures of connectedness was developed and tested: connectivity, global connectivity density, and local connectivity density. Global three-dimensional connectivity ranged from 904 to 1,607 connections. Global connectivity density ranged from 2.9 to 4.7 connections per mm with large intersubject differences. We found a decrease of local connectivity density with growing distance from the joint ranging from 5.1 to 0.2 connections per mm. These preliminary results represent a quantitative description of the well-known rarefication of the trabecular network when moving from epiphysis to the diaphysis. Three-dimensional visualization showed a dense network consisting mostly of rod-like trabeculae at the epiphysis changing to a less dense network of a few plate-like structures near the medullary canal. An algorithm for the quantitative classification of trabecular architecture with regard to plate or rod-like shape was tested for feasibility. We conclude that in vivo assessment of three-dimensional properties of the trabecular network is possible in human phalanges. Determination of connectivity and shape will allow quantification of structural aspects of osteoporotic changes and may improve assessment of fracture risk.

Adult↗

The functional logic of cortico-pulvinar connections.

The pulvinar is an 'associative' thalamic nucleus, meaning that most of its input and output relationships are formed with the cerebral cortex. The function of this circuitry is little understood and its anatomy, though much investigated, is notably recondite. This is because pulvinar connection patterns disrespect the architectural subunits (anterior, medial, lateral and inferior pulvinar nuclei) that have been the traditional reference system. This article presents a simplified, global model of the organization of cortico-pulvinar connections so as to pursue their structure-function relationships. Connections between the cortex and pulvinar are topographically organized, and as a result the pulvinar contains a 'map' of the cortical sheet. However, the topography is very blurred. Hence the pulvinar connection zones of nearby cortical areas overlap, allowing indirect transcortical communication via the pulvinar. A general observation is that indirect cortico-pulvino-cortical circuits tend to mimic direct cortico-cortical pathways: this is termed 'the replication principle'. It is equally apt for certain pairs (or groups) of nearby cortical areas that happen not to connect with each other. The 'replication' of this non-connection is achieved by discontinuities and dislocations of the cortical topography within the pulvinar, such that the associated pair of connection zones do not overlap. Certain of these deformations can be used to divide the global cortical topography into specific sub-domains, which form the natural units of a connectional subdivision of the pulvinar. A substantial part of the pulvinar also expresses visual topography, reflecting visual maps in occipital cortex. There are just two well-ordered visual maps in the pulvinar, that both receive projections from area V1, and several other occipital areas; the resulting duplication of cortical topography means that each visual map also acts as a separate connection domain. In summary, the model identifies four topographically ordered connection domains, and reconciles the coexistence of visual and cortical maps in two of them. The replication principle operates at and below the level of domain structure. It is argued that cortico-pulvinar circuitry replicates the pattern of cortical circuitry but not its function, playing a more regulatory role instead. Thalamic neurons differ from cortical neurons in their inherent rhythmicity, and the pattern of cortico-thalamic connections must govern the formation of specific resonant circuits. The broad implication is that the pulvinar acts to coordinate cortical information processing by facilitating and sustaining the formation of synchronized trans-areal assemblies; a more pointed suggestion is that, owing to the considerable blurring of cortical topography in the pulvinar, rival cortical assemblies may be in competition to recruit thalamic elements in order to outlast each other in activity.

Brain Mapping↗

Highly nonrandom features of synaptic connectivity in local cortical circuits.

How different is local cortical circuitry from a random network? To answer this question, we probed synaptic connections with several hundred simultaneous quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual cortex. Analysis of this dataset revealed several nonrandom features in synaptic connectivity. We confirmed previous reports that bidirectional connections are more common than expected in a random network. We found that several highly clustered three-neuron connectivity patterns are overrepresented, suggesting that connections tend to cluster together. We also analyzed synaptic connection strength as defined by the peak excitatory postsynaptic potential amplitude. We found that the distribution of synaptic connection strength differs significantly from the Poisson distribution and can be fitted by a lognormal distribution. Such a distribution has a heavier tail and implies that synaptic weight is concentrated among few synaptic connections. In addition, the strengths of synaptic connections sharing pre- or postsynaptic neurons are correlated, implying that strong connections are even more clustered than the weak ones. Therefore, the local cortical network structure can be viewed as a skeleton of stronger connections in a sea of weaker ones. Such a skeleton is likely to play an important role in network dynamics and should be investigated further.

Animals↗

Organization of long-range inhibitory connections with rat visual cortex.

We have studied the laminar organization of local long-range inhibitory connections within rat primary visual cortex (area 17) by combining retrograde tracing of nerve cell bodies with glutamic acid decarboxylase immunocytochemistry. While most inhibitory connections are confined to within 0.4 mm of the injection site, a subset of neurons at the layer 5/6 border provide long-range (> 1 mm) inhibitory connections within area 17. However, other cell layers that contain similar local long-range horizontal connections, that is, lower layer 2/3, upper layer 5, and lower layer 6 (Burkhalter and Charles, 1990), show a much more restricted distribution of inhibitory connections. This suggests that cells at the layer 5/6 border play a role in the direct inhibition of neurons at a distant point of the topographic map. Similar double labeling studies reveal long-range inhibitory connections between visual areas. Following injections of fluorescent tracers into area 17, in horizontal sections inhibitory connections can be identified that are up to 8 mm long, linking the extrastriate subdivisions 18a and 18b with striate cortex. Conversely, injections of fluorescent tracers into the cytoarchitectonic subdivision 18a reveal local long-range inhibitory connections within 18a, long-range inhibitory connections between 18a and the cytoarchitectonic subdivision 18b, and inhibitory forward connections from area 17 to 18a. These results suggest that the communication between different cortical areas can be influenced by direct inhibitory connections.

Animals↗

Connections of visual areas of the upper temporal lobe of owl monkeys: the MT crescent and dorsal and ventral subdivisions of FST.

An oval of cortex of moderately dense myelination just ventral to the middle temporal visual area (MT) with input from MT has been referred to as the fundal area of the superior temporal sulcus (FST). Injections of the tracer WGA-HRP into dorsal (FSTD) and ventral (FSTv) halves of FST revealed that only FSTD has connections with MT. FSTv has connections instead with small patches of cortex that string together like beads to form a ring or crescent (MTc) around most of MT. The patches in MTc stain densely for myelin or cytochrome oxidase, and they are embedded in a less densely stained matrix. The connections of FSTD associate the area with the dorsal stream of processing directed toward posterior parietal cortex and important in spatial aspects of vision. Thus, FSTD has direct connections with ventral posterior parietal cortex (VPP), and connections with MT, the medial superior temporal (MST), and dorsomedial (DM) visual areas, all areas that relay to posterior parietal cortex. In contrast, FSTv does not appear to have connections with either VPP or MST, and only sparse connections with DM. Rather, major connections of FSTv are with inferior temporal cortex. Thus, FSTv is more associated with the ventral stream of processing related to object vision. However, both FSTv and FSTD have connections with area 18 or V-II, the dorsolateral visual area, the frontal eye field, and a frontal visual area. Interhemispheric connections of FSTD include FSTD, MT, and MST, while interhemispheric connections of FSTv include FSTv and MTc.

Animals↗

Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.

BACKGROUND/AIMS: Connective tissue growth factor is a recently described mitogenic protein implicated in a variety of fibrotic disorders. Connective tissue growth factor may be a downstream mediator of the pro-fibrotic and mitogenic actions of transforming growth factor-beta, promoting extracellular matrix deposition and fibrogenesis. As transforming growth factor-beta is considered important to the pathogenesis of hepatic fibrosis, we examined the possible contribution of connective tissue growth factor to this process. METHODS: Connective tissue growth factor expression was examined in normal and fibrotic human and rat livers using RT-PCR and ribonuclease protection assays, and in primary cultures of rat hepatic stellate cells by Northern and Western blotting. RESULTS: Ribonuclease protection assays demonstrated connective tissue growth factor mRNA was increased 3-5-fold in human fibrotic liver compared with normal. RT-PCR showed this mRNA was increased in carbon-tetrachloride-treated rat liver. Northern analysis showed connective tissue growth factor mRNA was increasingly expressed during progressive activation of cultured rat hepatic stellate cells. Western analysis confirmed that freshly isolated hepatic stellate cells secreted relatively little connective tissue growth factor compared with hepatic stellate cells activated in culture. Hepatic stellate cells stimulated with transforming growth factor-beta showed increased expression of connective tissue growth factor mRNA and protein. CONCLUSIONS: Connective tissue growth factor mRNA is consistently upregulated in human liver cirrhosis of various aetiologies, supporting a role for this growth factor in hepatic fibrogenesis. Our studies suggest that hepatic stellate cells may be an important source of hepatic connective tissue growth factor in vivo, particularly following stimulation with transforming growth factor-beta.

Animals↗

The role of connective tissue in inhibiting epithelial downgrowth on titanium-coated percutaneous implants.

Ideally, the surface of epithelium-penetrating implants should impede apical epithelial migration. Previous studies have shown that micromachined grooved surfaces can produce connective-tissue ingrowth, which inhibits epithelial downgrowth on percutaneous implants [Chehroudi et al., J. Biomed. Mater. Res., 24, 9, (1990)]. However, in those studies, connective tissue and epithelium interacted with the same surface so that the effects of the surfaces on each population could not be determined separately. The objectives of this study were (a) to examine cell behavior on implants in which connective tissue contacted surfaces of various topographies and epithelium encountered only a smooth surface, and (b) to compare one-stage and two-stage surgical techniques. Implants had a base component (BC) which was either smooth or had a surface with 19-micron- or 30-micron-deep grooves or 120-micron-deep tapered pits, and a skin-penetrating component (SPC) which was smooth. In the two-stage technique, the BC was implanted subcutaneously for 8 weeks, which permitted the healing of the peri-implant connective tissue. In the second stage the SPC was connected to the BC. For one-stage implants, BC & SPC were connected and implanted percutaneously. Implants (BC & SPC) were removed 1, 2, or 3 weeks after percutaneous implantation and histological sections were measured for recession, connective tissue and epithelial attachment as well as capsule thickness. Light microscopy indicated that both grooved and tapered pitted surfaces encouraged connective tissue ingrowth. On the grooved surfaces, the orientation of fibroblasts changed from an oblique to a more complex pattern which included cells having round nuclei within the grooves, as well as cells oriented oblique or perpendicular to the grooves. In the tapered pits a hammock-like arrangement of fibroblasts was observed. In some cases, foci of mineralization and formation of bonelike tissue were found on the grooved and pitted surfaces. The apical migration of the epithelium was significantly (p less than 0.05) inhibited by those micromachined surfaces which produced connective tissue ingrowth to the BC. This study found that placing the implants in two stages improved the performance of percutaneous devices, and that a further improvement was achieved if the implant had a surface promoting connective tissue ingrowth.

Animals↗

The influence of differing connective tissue substrates on the maintenance of adult stratified squamous epithelia.

The interaction between adult stratified squamous epithelium and its supporting connective tissue possibly involves both permissive and directive influences. To examine the effect of vitality and specificity of connective tissue on the maintenance of epithelial structure and histodifferentiation, specimens of skin and oral mucosa from various regions of adult mice were separated using either EDTA or trypsin. Prior to transplantation, the epithelium was recombined with either inverted homologous connective tissue or with connective tissue that had been killed either by heating or repeated freeze-thawing. Epithelial sheets were also transplanted onto the graft bed alone or in combination with striated muscle or tendon. Normal patterns of cytodifferentiation were maintained when the epithelium was recombined with inverted or frozen-thawed subepithelial connective tissue but there was a loss of spatial organization on the frozen-thawed connective tissue. In contrast, heat-killed or trypsin-treated frozen-thawed subepithelial connective tissue and non-dermal connective tissue failed to maintain a viable epithelium. These observations suggest that subepithelial connective tissues (dermis, lamina propria) but not deep connective tissues facilitate epithelial proliferation and histodifferentiation.

Animals↗

Silicone breast implants and the risk of connective-tissue diseases and symptoms.

BACKGROUND: Silicone breast implants have been linked to a variety of illnesses, the most controversial of which are connective-tissue diseases and symptoms. To study this relation, we analyzed data from 14 years of follow-up of the Nurses' Health Study cohort. METHODS: Women who were free from connective-tissue disease in June 1976 were followed through May 31, 1990, before there was widespread media coverage of the possible association of breast implants and connective-tissue diseases. Information was collected through biennial and supplementary mailed questionnaires and blinded reviews of medical records with the use of standardized criteria. Relative risk, the measure of association, was defined as the incidence rate of connective-tissue disease among women with breast implants divided by the corresponding incidence rate among women without breast implants. RESULTS: Among 87,501 women who were eligible for follow-up, 516 were confirmed as having definite connective-tissue diseases and 1183 as having breast implants (of which 876 were silicone-gel-filled, 170 saline-filled, 67 double-lumen, 14 polyurethane-coated, and 56 of unknown type). The mean (+/- SD) period of follow-up after surgery was 9.9 +/- 6.4 years (range, 1 month to 40.5 years). Three of the patients with definite connective-tissue disease--all had rheumatoid arthritis--had implants (one silicone-gel-filled, one saline-filled, and one double-lumen). The age-adjusted relative risk of a definite connective-tissue disease among women with any type of implant was 0.6 (95 percent confidence interval, 0.2 to 2.0), as compared with women without implants. For women with silicon-gel-filled implants, the comparable relative risk was 0.3 (95 percent confidence interval, 0 to 1.9). The relative risk of self-reported signs or symptoms of connective-tissue disease for women with implants was 1.5 (95 percent confidence interval, 0.9 to 2.4); the risk of having any 1 of 41 signs, symptoms, or laboratory features of connective-tissue disease was 0.7 (95 percent confidence interval, 0.3 to 1.6). CONCLUSIONS: In a large cohort study, we did not find an association between silicone breast implants and connective-tissue diseases, defined according to a variety of standardized criteria, or signs and symptoms of these diseases.

Adult↗

The prognostic value of nailfold capillary changes for the development of connective tissue disease in children and adolescents with primary raynaud phenomenon: a follow-up study of 250 patients.

To assess the prognostic value of capillaroscopy findings for the development of connective tissue disease in children and adolescents with Raynaud phenomenon, we followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first capillaroscopy was performed. Every 6 months they were screened for signs and symptoms of connective tissue disease. Analysis was performed on capillary changes registered 6 months before the development of connective tissue disease. Capillary changes were classified into three types: normal, nonspecific, and sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis of a specific connective tissue disease. Systemic lupus erythematosus was found in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 13 (5.2%). The mean time for the evolution of Raynaud phenomenon into undifferentiated connective tissue disease or a form of the disease was 2 years. Most of the subjects with primary Raynaud phenomenon (173/191, 91%), undifferentiated connective tissue disease (22/27, 81%), juvenile onset rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9 (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of all the subjects, only 10 (4%) showed sclerodermatous disease type capillary changes 6 months before the expression of a particular disease: eight (62%) of these developed scleroderma spectrum disorders, one expressed systemic lupus erythematosus, and one had undifferentiated connective tissue disease. We concluded that there were no specific capillary changes predictive for future development of systemic lupus erythematosus, juvenile onset rheumatoid arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in children and adolescents with Raynaud phenomenon. Most of our study subjects with Raynaud phenomenon who developed these diseases had normal capillary findings or nonspecific changes. Children and adolescents who developed scleroderma spectrum disorders showed a sclerodermatous type of capillary changes 6 months before the expression of the disease, indicating that this type of capillary changes in children and adolescents with Raynaud phenomenon highly correlated with further development of scleroderma spectrum disorders.

Adolescent↗

[Three-dimensional architecture of the connective tissue papillae of the mouse tongue as viewed by scanning electron microscopy].

The morphological relationship between lingual papillae and underlying connective tissue papillae of mouse was studied because it is conceivable that the differentiation of epithelium may be affected by its connective tissue. Tongues of adult male mice were fixed in formol or Karnovsky's fixative. After removal of the epithelium by long-term hydrochloric acid treatment at room temperature, the surface of the connective tissue papillae was observed by scanning electron microscopy. Connective tissue papillae that were fungiform in shape and which were distributed at the anterior part of the tongue showed barnacle-like protrusion after removal of the epithelium. Their surface was covered by numerous long filaments running vertically and there was a round depression on the top of each fungiform papilla that may be found to correspond to a taste bud when the results of light and electron microscopy are compared. Filiform papillae in a narrow sense were closely distributed in the anterior part of the tongue. They had a tapered tip declining posteriorly. Each filiform connective tissue papilla was conical in shape and had a round depression that slightly declined antero-downward, and a long narrow depression ran along the anterior edge of each connective tissue papilla. Large conical papillae which distributed at the anterior margin of the intermolar prominence had shovel-like connective tissue papillae which had a depression at the posterior surface unlike that of the filiform papillae. Branched papillae distributed in the posterior part of the prominence had a depression at the anterior surface. Under the light microscope, numerous keratohyaline granules were seen to be contained only in the posterior epithelial cell line of the large conical papillae distributed in the anterior margin of the prominence, while these granules were found only in the anterior epithelial cell line of both filiform and branched papillae. It became clear that the axes of each connective tissue papilla of large conical papillae distributed radically around a single midpoint. Connective tissue papillae of vallate papillae had a beehive-like shape and in follicate papillae there were several vertical elliptical gaps, seen when the epithelium was peeled from the connective tissue.

Animals↗

[New results on ageing of connective tissue (author's transl)].

Some new results on ageing of connective tissue are demonstrated, regarding not only mesenchymal, but also parenchymal organs of human and rat (both sexes). These results show that ageing of connective tissue is more a dynamic process (with measurable metabolic parameters of the several connective tissue cells and their products) than a passive or so-called degenerative connective tissue process. The bradytrophy concept of connective tissue cannot be accepted any longer. Then connective tissue cells can produce metabolic rates of the same level like parenchymal cells. The different organs possess partly common basic processes partly differences in connective tissue ageing, dependent on the composition and patterns of proteoglycans resp. of GAG and collagen types, furthermore dependent on localisation, structure and function. The results on ageing of connective tissue are useful for better understanding of ageing processes of parenchymal organs. Then their ageing is influenced essentially by the ageing of the own connective tissues. The turnover, more than the number of mesenchymal and parenchymal cells, decreases with ageing. More old than young cells seem to exist in old tissues and organs. The performance of ageing connective tissue cells can be constant or increase or decrease. Many mesenchymal and parenchymal organs develop a so-called "ageing-fibrosis".

Aged↗

Perirhinal and postrhinal cortices of the rat: interconnectivity and connections with the entorhinal cortex.

The cortical regions dorsally adjacent to the posterior rhinal sulcus in the rat can be divided into a rostral region, the perirhinal cortex, which shares features of the monkey perirhinal cortex, and a caudal region, the postrhinal cortex, which has connectional attributes similar to the monkey parahippocampal cortex. We examined the connectivity among the rat perirhinal (areas 35 and 36), postrhinal, and entorhinal cortices by placing anterograde and retrograde tracers in all three regions. There is a dorsal-to-ventral cascade of connections in the perirhinal and entorhinal cortices. Dorsal area 36 projects strongly to ventral area 36, and ventral area 36 projects strongly to area 35. The return projections are substantially weaker. The cascade continues with the perirhinal to entorhinal connections. Area 35 is more strongly interconnected with the entorhinal cortex, ventral area 36 somewhat less strongly, and dorsal area 36 projects only weakly to the entorhinal cortex. The postrhinal-to-perirhinal connections also follow this general pattern. The postrhinal cortex is more heavily connected with dorsal area 36 than with ventral area 36 and is more heavily connected with area 36 than with area 35. The rostral portion of the postrhinal cortex has the strongest connections with the perirhinal cortex. Like in the monkey, the perirhinal and postrhinal cortices have different patterns of projections to the entorhinal cortex. The perirhinal cortex is preferentially connected with the rostrolateral portion of the entorhinal cortex. The postrhinal cortex projects to a part of this same region but is also connected to caudal and redial portions of the entorhinal cortex. The perirhinal and postrhinal projections to the entorhinal cortex originate in layers III and V and terminate preferentially in layers II and III.

Animals↗

Frontal eye field as defined by intracortical microstimulation in squirrel monkeys, owl monkeys, and macaque monkeys. II. Cortical connections.

Physiological (intracortical microstimulation) and anatomical (transport of horseradish peroxidase conjugated to wheat germ agglutinin as shown by tetramethyl benzidine) approaches were combined in the same animals to reveal the locations, extents, and cortical connections of the frontal eye fields (FEF) in squirrel, owl, and macaque monkeys. In some of the same owl and macaque monkeys, intracortical microstimulation was also used to evoke eye movements from dorsomedial frontal cortex (the supplementary motor area). In addition, in all of the owl and squirrel monkeys, intracortical microstimulation was also used to evoke body movements from the premotor and motor cortex situated between the central dimple and the FEF. These microstimulation data were directly compared to the distribution of anterogradely and retrogradely transported label resulting from injections of tracer into the FEF in each monkey. Since the injection sites were limited to the physiologically defined FEF, the demonstrated connections were solely those of the FEF. To aid in the interpretation of areal patterns of connections, the relatively smooth cortex of owl and squirrel monkeys was unfolded, flattened, and cut parallel to the flattened surface. Cortex of macaque monkeys, which has numerous deep sulci, was cut coronally. Reciprocal connections with the ipsilateral frontal lobe were similar in all three species: dorsomedial cortex (supplementary motor area), cortex just rostral (periprincipal prefrontal cortex) to the FEF, and cortex just caudal (premotor cortex) to the FEF. In squirrel and owl monkeys, extensive reciprocal connections were made with cortex throughout the caudal half of the lateral fissure and, to a much lesser extent, cortex around the superior temporal sulcus. In macaque monkeys, only sparse connections were present with cortex of the lateral fissure, but extensive and dense connections were made with cortex throughout the caudal one-third to one-half of the superior temporal sulcus. In addition, very dense reciprocal connections were made with the cortex of the lateral, or inferior, bank of the intraparietal sulcus. Contralateral reciprocal connections in all three species were virtually limited to regions that correspond in location to the FEF and the supplementary motor area. The results of this study reveal connections between the physiologically defined frontal eye field and cortical regions known to participate in higher order visual processing, short-term memory, multimodal, visuomotor, and skeletomotor functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Connections between area 3b of the somatosensory cortex and subdivisions of the ventroposterior nuclear complex and the anterior pulvinar nucleus in squirrel monkeys.

The goal of this study was to determine whether somatosensory thalamic nuclei other than the ventroposterior nucleus proper (VP) have connections with area 3b of the postcentral cortex in squirrel monkeys. Small injections of the anatomical tracers wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) or 3H-proline were placed in electrophysiologically identified representations of body parts. The results indicate that, besides the well-established somatotopically organized connections with VP, area 3b has connections with three other nuclei of the somatosensory thalamus: the ventroposterior superior nucleus (VPS ["shell" of VP]), the ventroposterior inferior nucleus (VPI), and the anterior pulvinar nucleus (Pa). Injections confined to area 3b or involving adjacent parts of area 3a or area 1 indicate that connections between VPS, VPI, and Pa and the postcentral cortex are somatotopically organized. In VPS, connections related to the hand were found medially, and connections related to the foot were lateral. In VPI, connections with the cortical representations of the mouth, hand, and foot were successively more lateral. In Pa, connections related to the mouth, hand, and foot were successively more ventral, lateral, and caudal, and the trunk region was caudomedial. The findings suggest that VPI contains a representation of all parts of the body, including the face. The connections of Pa with the primary somatosensory cortex, area 3b, the location of Pa relative to the ventroposterior nucleus, and the high degree of topographic order in the connections of Pa with the postcentral cortex suggest that Pa is an integral part of the somatosensory thalamus in monkeys and is homologous to the medial nucleus of the posterior group (Pom) in other mammals. Overall, the results contribute to the growing evidence that individual somatosensory cortical areas in monkeys receive inputs from multiple thalamic sources, and that a single thalamic nucleus has several cortical targets.

Animals↗

Cortical connections of dorsal cortex rostral to V II in squirrel monkeys.

A region of dorsal cortex along the rostral border of V II has been described as comprising a visual area or areas separate from more lateral cortex in both New and Old World primates. To evaluate these possibilities in squirrel monkeys, we studied patterns of cortical connections by injecting Fast Blue, Fluoro-Gold, horseradish peroxidase, and wheat germ agglutinin conjugated to horseradish peroxidase into the dorsal region and related results to distinctions in myeloarchitecture. Our major conclusions are as follows. 1) The dorsal region (D) has distinctly different connections from the area found laterally, the caudal subdivision of the dorsolateral area (DLC). These include major connections with the rostral subdivision of the dorsolateral area (DLR), ventral posterior parietal cortex in the Sylvian fissure, the middle temporal area (MT), the medial superior temporal area (MST), ventral cortex just rostral to V II, and cortex in the inferior temporal sulcus. Weaker connections are with V I, V II, DLC, the fundal superior temporal area (FST), and the frontal lobe. In contrast, DLC has strong connections with V II and inferior temporal (IT) cortex, weaker connections with DLR, and lacks connections with ventral posterior parietal cortex (Steele et al: J Comp Neurol 306:495-520, 1991). 2) Caudal and rostral aspects of dorsal cortex differ in the magnitude of connections with V I, V II, DLR, and FST. These differences are consistent with the previous proposal that at least two visual areas, caudal and rostral, occupy the dorsal region in squirrel monkeys (Krubitzer and Kaas: Visual Neurosci 5:165, 1990), but they could also reflect regional differences in the connections of a single visual area. 3) The dorsal region is more densely myelinated than surrounding cortex; however, rostral aspects of dorsal cortex are less myelinated than caudal aspects, again suggesting the existence of at least two areas. 4) The distinctiveness of connections between dorsal cortex and rostral as compared to caudal dorsolateral cortex provides further evidence for dividing the region of DL into two visual areas, DLC and DLR (Cusick and Kaas: Visual Neurosci 1:211, 1988; Steele et al: J Comp Neurol 306:495-520, 1991).

Amidines↗

Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei.

The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control.

Animals↗

Rapid rearrangement of intrinsic tangential connections in the striate cortex of normal and dark-reared kittens: lack of exuberance beyond the second postnatal week.

Clustered intrinsic connections in the kitten striate cortex originate from an unclustered, diffusely organized pattern prevailing during the first postnatal week. We have studied the progress of this reorganization and its dependence on visual input by determining the topographies of the intrinsic tangential connections at various postnatal ages by means of axonal tracing methods. Neurons were labeled either by diffusion of the carbocyanin dye DiI in animals ranging in age between 1 day and 30 days, or by retrograde transport of fluorescent microspheres in animals ranging in age between 7 days and 11 months. Quantitative evaluation of retrogradely labeled neurons revealed that during the first postnatal week, intrinsic tangential connections are organized in an unclustered fashion. During the second postnatal week a rapid rearrangement of connections occurs and is complete around postnatal day 11. The main events taking place during the course of this rearrangement are a decrease in the density of tangential connections and an arrangement of them in a clustered fashion. Once the clusters have been formed, the periodicity of the clustered pattern of connections and the size and distinctness of the clusters do not change. This means that the system of clustered tangential connections is adult-like at the end of the second postnatal week. Dark rearing affects neither the rapid rearrangement of horizontal connections into an adult-like system of clusters, nor the integrity of this clustered topography until the end of the first postnatal month. The overall distribution and the lateral extent of the tangential connections remain about the same during the postnatal period and are not affected by dark rearing until the end of the first postnatal month. We conclude that the clustered system of tangential connections in the cat's striate cortex is determined innately.

Aging↗