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Clinical usefulness of antibodies to U1snRNP proteins in mixed connective tissue disease and systemic lupus erythematosus.

OBJECTIVES: To determine whether the anti-68 kDaU1snRNP antibody is associated with mixed connective tissue disease and not with SLE; to evaluate correlations between anti-U1snRNP titers and disease activity; and to look for associations between anti-U1snRNP specificities and specific clinical features. PATIENTS AND METHODS: 40 patients with a positive double diffusion test for anti-68 kDa U1snRNP were studied, including 21 with mixed connective tissue disease, 14 with systemic lupus erythematosus and five with other connective tissue diseases. IgGs to 68 kDa U1snRNP were assayed using an ELISA. Clinical features, disease activity and antibody test findings were evaluated longitudinally in nine patients. RESULTS: Both proportions of patients with anti-68 kDa U1snRNP and titers of IgG to 68 kDa U1snRNP were similar in the mixed connective tissue disease and systemic lupus erythematosus groups. Patients with mixed connective tissue disease were significantly more likely to have anti-A U1snRNP or anti-C U1snRNP than those with systemic lupus erythematosus (P < 0.03 and P < 0.04, respectively). No significant correlations were found between any of the features of mixed connective tissue disease (e.g., Raynaud's phenomenon, myositis, or sausage digits) and a specific anti-U1snRNP antibody. During follow-up (mean, seven years; range, 1-25 years), changes occurred in the anti-U1snRNP profile and in the anti-68 kDa U1snRNP titer. These changes were not correlated with disease activity. CONCLUSIONS: IgGs to 68 kDa U1snRNP are not associated with a specific pattern of anti-RNP-positive connective tissue disease. No useful information can be gained by monitoring anti-68 kDa U1snRNP IgG titers over time. A Western blot profile including anti-A U1snRNP or anti-C U1snRNP indicates a high likelihood of U1snRNP-associated mixed connective tissue syndrome (MCTD).

Adolescent↗

Microcircuitry of forward and feedback connections within rat visual cortex.

Visual cortex in mammals is composed of many distinct areas that are linked by reciprocal connections to form a multilevel hierarchy. Ascending information is sent via forward connections from lower to higher areas and is thought to contribute to the emergence of increasingly complex receptive field properties at higher levels. Descending signals are transmitted via feedback connections from higher to lower areas and are believed to provide information about the context in which a stimulus appears, to contribute to modulation of visual responses by attention, and to play a role in memory processes. To determine whether forward and feedback pathways in rat visual cortex constitute distinct intracortical circuits, we have studied the distribution of reciprocal corticocortical inputs to pyramidal cells and gamma-aminobutyric acid (GABA)ergic interneurons. For this purpose, we chose forward and feedback connections between primary visual cortex and the secondary extrastriate lateromedial (LM) area as a model system. Pathways were traced with the axonal marker phaseolus vulgaris-leucoagglutinin. Labeled terminals were identified in the electron microscope, and GABA immunocytochemistry was used to identify the postsynaptic dendritic shafts of GABAergic interneurons. In both pathways, inputs to pyramidal cells were directed preferentially to dendritic spines and not to shafts. In the forward pathway, 90% of labeled inputs were distributed to pyramidal cells and 10% to interneurons. This proportion was similar to that of nearby unlabeled connections in the neuropil, indicating that forward connections are not selective for pyramidal cells or interneurons. In sharp contrast, feedback connections were significantly different from the unlabeled connections and supplied almost exclusively pyramidal cells (98%). Feedback inputs to GABAergic neurons were five times weaker (2%) relative to the forward direction. These structural differences suggest that disynaptic GABAergic inhibition is much stronger in forward than in feedback pathways. Recent physiological experiments have confirmed this prediction (Shao et al. [1995] Soc. Neurosci. Abstr., 21:1274) and we, therefore, conclude that relatively small anatomical differences in the microcircuitry can have important functional consequences. It remains an open question whether generally reciprocal interareal circuits at all levels of the cortical hierarchy are organized in similar fashion.

Animals↗

Reciprocal entorhinal-hippocampal connections established by human fetal midgestation.

Little is known about the timing or sequence of genesis of connections between different areas of the developing human cerebral cortex. It has been shown that connections between areas V1 and V2 of the visual isocortex are established at about 37 weeks of gestation (Burkhalter [1993] Cerebr. Cortex 3:476-487), suggesting that cortico-cortical connections appear late in the 40-week human gestational period. However, there are indications from other studies that connections between subdivisions of the hippocampal formation may be established much earlier, by about 20 weeks of human gestation. To investigate this possibility, the lipophilic bidirectional tracer 1,1' dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate (DiI) was used to study connections between the entorhinal cortex, hippocampus, and temporal lobe neocortex in paraformaldehyde-fixed postmortem fetal tissue. The DiI transport revealed robust reciprocal connections between the entorhinal cortex, hippocampus, and subiculum, which were consistently present at 19 weeks of gestation (the earliest age studied), and which were anatomically similar to those in adult primates. Specifically, projections to the hippocampus and subiculum originated from neurons in the entorhinal cortex (EC) layers 2 and 3, whereas reciprocal projections to the EC originated from pyramidal neurons in the cornu ammonis region CA1 and the subiculum. In contrast, the perforant pathway projection from EC to the dentate gyrus, and all connections with the neocortex, reached only rudimentary stages of development by 22 weeks of gestation (the latest age studied). These findings suggest that hippocampal pathways develop prior to isocortical pathways, and that reciprocal entorhinal-hippocampal projections may be among the first cortico-cortical connections to be established in the human brain.

Brain↗

How do brain tumors alter functional connectivity? A magnetoencephalography study.

OBJECTIVE: This study was undertaken to test the hypothesis that brain tumors interfere with normal brain function by disrupting functional connectivity of brain networks. METHODS: Functional connectivity was assessed by computing the synchronization likelihood in a broad band (0.5-60Hz) or in the gamma band (30-60Hz) between all pairwise combinations of magnetoencephalography signals. Magnetoencephalography recordings were made at rest in 17 brain tumor patients and 15 healthy control subjects. For a given threshold of synchronization likelihood values, graphs of the suprathreshold connections between each magnetoencephalography channel and the others channels were built. RESULTS: In some regions, a variable number of channels without connectivity (missing connective points) at this threshold was found. The number of missing connective points was higher in patients with brain tumors than in control subjects (p < 0.0001, broad and gamma band) and was higher for left-sided than right-sided tumors (p = 0.008, broad band; p < 0.0001, gamma band). Individual results analysis indicates that the majority of brain tumor patients display several regions with missing connective point alterations in the affected and in the contralateral hemisphere. INTERPRETATION: Our findings suggest that brain tumors induce a loss of functional connectivity that affects multiple brain regions, and that left side brain tumors have the more severe consequences in this respect.

Adult↗

Functional connectivity networks are disrupted in left temporal lobe epilepsy.

OBJECTIVE: Functional connectivity maps the distributed network of brain regions fluctuating synchronously during a continuous brain state. This study sought to investigate whether patients with left temporal lobe epilepsy (TLE) differ from controls in their resting-state functional connectivity between typical language regions. METHODS: We studied 17 patients with left TLE, together with eight healthy controls, using seeded functional connectivity. Seed regions were defined using the regions of maximal activation and deactivation during a language functional magnetic resonance imaging (fMRI) task in a separate cohort of 30 controls. RESULTS: Language fMRI produced the expected activation pattern, which was not different between patients and controls. However, functional connectivity between language areas during rest was markedly different; whereas controls showed connectivity between each of the seed areas and the majority of the language areas, patients showed connectivity only with a few areas, particularly the seed area itself. This difference was significant in the direct comparison of patients and control connectivity maps. INTERPRETATION: We suggest that this reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of the language network during resting state in patients and may be related to subtle language difficulties in this patient population.

Adult↗

Molecular tectonics of metal-organic frameworks (MOFs): a rational design strategy for unusual mixed-connected network topologies.

To systematically explore the higher-dimensional network structures with mixed connectivity, a series of two-dimensional (2D) and three-dimensional (3D) metal-organic frameworks (MOFs) with unusual (3,6)-connected net topologies are presented. These crystalline materials include [{[Mn(btza)2(H2O)2].2 H2O}n] (1), [{[Zn(btza)2(H2O)2].2 H2O}n] (2), [{[Cu(btza)2].H2O}n] (3), and [{[Cd(btza)2].3 H2O}n] (4), which have been successfully assembled through a predesigned three-connected organic component bis(1,2,4-triazol-1-yl)acetate (btza) with a variety of octahedral metal cores based on the modular synthetic methodology. The topological paradigms shown in this work cover the 2D CdCl2, 3D (4(2).6)2(4(4).6(2).8(7).10(2)), and pyrite (pyr) types. That is, when properly treated with the familiar first-row divalent metal ions, btza may perfectly furnish the coordination spheres for effective connectivity to result in diverse (3,6)-connected nets. Beyond this, a detailed analysis of network topology for all known 3D (3,6)-connected frameworks in both inorganic and inorganic-organic hybrid materials is described. Specific network connectivity of these MOFs indicates that the metal centers represent the most significant and alterable factor in structural assembly, although they show reliable and similar geometries. In this context, the combination of the distinct d10 AgI ion with btza in different solvents affords two isomorphous MOFs [{[Ag(btza)].glycol}n] (5) and [{[Ag(btza)]CH3OH}n] (6) with a binodal 4-connected 3D SrAl2 (sra) topology. The network structures of MOFs 1-3 and 5 turn out to be more complicated and interesting if one considers the hydrogen bonding between the host coordination frameworks and the intercalated solvent molecules. Furthermore, the role of the included solvents in the generation and stabilization of MOFs 1-6 is also investigated.

Journal Article↗

Pulvinar and other subcortical connections of dorsolateral visual cortex in monkeys.

The present study used injections of neuroanatomical tracers to determine the subcortical connections of the caudal and rostral subdivisions of the dorsolateral area (DL) and the middle temporal crescent area (MT(C)) in owl monkeys (Aotus trivirgatus), squirrel monkeys (Saimiri sciureus), and macaque monkeys (Macaca fascicularis and M. radiata). Emphasis was on connections with the pulvinar. Patterns of corticopulvinar connections were related to subdivisions of the inferior pulvinar (PI) defined by histochemical or immunocytochemical architecture. Connections of DL/MT(C) were with the PI subdivisions, PICM, PICL, and PIp; the lateral pulvinar (PL); and, more sparsely, the lateral portion of the medial pulvinar (PM). In squirrel monkeys, there was a tendency for caudal DL to have stronger connections with PICL than PICM and for rostral DL/MT(C) to have stronger connections with PICM than PICL. In all three primates, DL/MT(C) had reciprocal connections with the pulvinar and claustrum; received afferents from the locus coeruleus, dorsal raphe, nucleus annularis, central superior nucleus, pontine reticular formation, lateral geniculate nucleus, paracentral nucleus, central medial nucleus, lateral hypothalamus, basal nucleus of the amygdala, and basal nucleus of Meynert/substantia innominata; and sent efferents to the pons, superior colliculus, reticular nucleus, caudate, and putamen. Projections from DL/MT(C) to the nucleus of the optic tract were also observed in squirrel and owl monkeys. Similarities in the subcortical connections of the dorsolateral region, especially those with the pulvinar, provide further support for the conclusion that the DL regions are homologous in the three primate groups.

Animals↗

Corticopulvinar connections of areas V5, V4, and V3 in the macaque monkey: a dual model of retinal and cortical topographies.

The connection zones of cortical areas V3, V4, and V5 (MT) with the thalamic pulvinar nucleus in the macaque monkey were identified. A combination of single- and dual-tracer techniques was used to study their topography and to establish whether these zones occupy separate or overlapping pulvinar territories. In each case, the retinotopic distribution of tracer in the pulvinar was charted by reference to its parallel distribution within the maps of cortical areas V1 and V2. Each of the areas V3, V4, and V5 were found to connect with both the 1° and the 2° maps located within the inferior and lateral pulvinar nuclei and to respect the previously identified topographies of these maps. However, V5 connects to a narrow zone lining the rostrolateral margin of the lateral and inferior pulvinar and V4 to a broader zone within the body of these two nuclei, which is adjacent to but separate from the V5 zone; the V3 zone overlaps both. Focal injections into cortex produce columns of pulvinar label whose trajectory defines a line of isorepresentation. The lines of isorepresentation in the 1° and 2° maps are approximately linear and parallel and adopt a rostrolateral to caudomedial axis; in the 1° map, this axis is roughly perpendicular to the facet of the inferior pulvinar that lies adjacent to the lateral geniculate nucleus. The connections of V5 and V4 can be modelled as successive zones along the axis of isorepresentation, with registered visual topographies. The scheme is extended by existing reports that inferotemporal cortex connects to the caudomedial pole of this axis-reflecting an occipitotemporal cortical gradient, in that V1 and other prestriate areas, e.g., V3, connect to the opposite pole. Thus a simple model of the mapped volume in the pulvinar arises, in which a unidimensional cortical topography is represented orthogonally to retinal topography. Adjoining this volume medially, within the inferior and medial pulvinar, is a second, heavier zone of V5 connectivity, which is poorly topographic. Both the medial and the rostrolateral zones of V5 connectivity may overlap with previously identified regions of tectal input to the pulvinar.

Animals↗

Experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). II: Dorsal area and preoptic region.

In this study and the accompanying article (Folgueira et al., 2004a), the fluorescent carbocyanine dye 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to comprehensively analyze the connections of the different regions of the telencephalic lobes and the preoptic region of the rainbow trout. Here, we analyze the connections of the dorsal area (D; pallium) of the telencephalon, and the preoptic region, as well as the telencephalic connections of several structures in the diencephalon and brainstem of juvenile trout. The dorsal plus dorsolateral pallial zone of D (Dd+Dl-d) receives afferents from contralateral Dd+Dl-d, the ventral area of the telencephalon, preoptic nucleus, suprachiasmatic nucleus, medial thalamus, preglomerular complex, anterior and lateral tuberal nuclei, posterior tuberal nucleus, posterior hypothalamic lobe, superior raphe nucleus, and the rhombencephalic central gray and reticular formation, and projects to the central zone of D (Dc), medial thalamus, and some caudomedial hypothalamic regions. The medial zone of D (Dm) maintains reciprocal connections with the preglomerular complex and also receives afferents from the preoptic nucleus, suprachiasmatic nucleus, anterior tuberal nucleus, preglomerular tertiary gustatory nucleus, posterior tubercle, superior raphe nucleus, locus coeruleus, and the rhombencephalic central gray, and reticular formation. Dc receives fibers mainly from Dd+Dl-d, preoptic nucleus, preglomerular complex, and torus semicircularis and projects to several extratelencephalic centers, including the paracommissural nucleus, optic tectum, torus semicircularis, thalamus, preglomerular complex, posterior tubercle nuclei, and inferior hypothalamic lobes. The posterior zone of D (Dp) is mainly connected with the olfactory bulbs, the ventral and supracommissural nuclei of the ventral area (subpallium), the preoptic nucleus, and the preglomerular complex and projects to wide hypothalamic and posterior tubercular regions. The preoptic nucleus projects to the olfactory bulb, to most regions of the telencephalic lobes, and to several diencephalic and brainstem structures. These results reveal complex and specialized connectional patterns in the rainbow trout dorsal telencephalon and preoptic region. Most of these connections have not been described previously in salmonids. These connections indicate that the salmonid telencephalon is involved in multisensorial processing and modulation of brain activity.

Animals↗

Intracortical connectivity of architectonic fields in the somatic sensory, motor and parietal cortex of monkeys.

Anterograde and retrograde transport methods were used to study the corticocortical connectivity of areas 3a, 3b, 1, 2, 5, 4 and 6 of the monkey cerebral cortex. Fields were identified by cytoarchitectonic features and by thalamic connectivity in the same brains. Area 3a was identified by first recording a short latency group I afferent evoked potential. Attempts were made to analyze the data in terms of: (1) routes whereby somatic sensory input might influence the performance of motor cortex neurons; (2) possible multiple representations of the body surface in the component fields of the first somatic sensory area (SI). Apart from vertical interlaminar connections, two types of intracortical connectivity are recognized. The first, regarded as "non-specific," consists of axons spreading out in layers I, III and V-VI from all sides of an injection of isotope; these cross architectonic borders indiscrimininately. They are not unique to the regions studied. The second is formed by axons entering the white matter and re-entering other fields. In these, they terminate in layers I-IV in one or more mediolaterally oriented strips of fairly constant width (0.5--1 mm) and separated by gaps of comparable size. Though there is a broadly systematic topography in these projections, the strips are probably best regarded as representing some feature other than receptive field position. Separate representations are nevertheless implied in area 3b, in areas 1 and 2 (together), in areas 3a and 4 (together) and in area 5; with, in each case, the representations of the digits pointed at the central sulcus. Area 3b is not connected with areas 3a or 4, but projects to a combined areas 1 and 2. Area 1 is reciprocally connected with area 3a and area 2 reciprocally with area 4. The connectivity of area 3a, as conventionally identified, is such that it is probably best regarded not as an entity, but as a part of area 4. Areas identified by others as area 3a should probably be regraded as parts of area 3b. Parts of area 5 that should be more properly considered as area 2, and other parts that receive thalamic input not from the ventrobasal complex but from the lateral nuclear complex and anterior pulvinar, are also interconnected with area 4. More posterior parts of area 5 are connected with laterally placed parts of area 6. A more medial part of area 6, the supplementary motor area, occupies a pivotal position in the sensory-motor cortex, for it receives fibers from areas 3a, 4, 1, 2 and 5 (all parts), and projects back to areas 3a, 4 and 5.

Animals↗

Patterns of connections from the striate cortex to cortical visual areas in superior temporal sulcus of macaque and middle temporal gyrus of owl monkey.

Double label-emulsion autoradiography has been used in rhesus monkeys to study cortico-cortical connections, arising from two separate sites of the striate cortex, and going in the same hemisphere into the cortex in the medial part of the posterior (or ventral) bank of the superior temporal sulcus (area STS). The projections from a single cortical locus are segregated into several patches of labeled terminals in layers III-IV, which form bands in consecutive sections. Fields of distribution of these bands from two sites of area 17 may completely overlap, when they arise from neighboring regions, or may partially overlap, when they arise from more separated regions. The latter show a retinotopical order in these connections and, consequently, of area STS itself: central visual field is lateral and ventral in STS to peripheral visual field, and upper visual field is ventral and medial to lower visual field. Connections from area 17 to area MT in owl monkey were analyzed in a comparative study. Results show that these connections are also highly segregated into bands, and that those arising in separate, but neighboring regions of 17, may greatly overlap in MT. The retinotopy of these connections was not studied, however. The similar divergent distribution of area 17 connections to STS and MT, and the similarity of the topography of STS connections and of the known retinotopy of area MT, are considered as elements of homologies between these areas. Functional implications of these divergent patterns of connections to these motion-sensitive areas (Zeki, '74), are considered.

Animals↗

Intrinsic laminar lattice connections in primate visual cortex.

Intracortical injections of horseradish peroxidase (HRP) reveal a system of periodically organized intrinsic connections in primate striate cortex. In layers 2 and 3 these connections form a reticular or latticelike pattern, extending for about 1.5-2.0 mm around an injection. This connectional lattice is composed of HRP-labeled walls (350-450 microns apart Saimiri and about 500-600 microns in macaque) surrounding unlabeled central lacunae. Within the lattice walls there are regularly arranged punctate loci of particularly dense HRP label, appearing as isolated patches as the lattice wall labeling thins further from the injection site. A periodic organization has also been demonstrated for the intrinsic connections in layer 4B, which are apparently in register with the supragranular periodicities, although separated from these by a thin unlabeled region. The 4B lattice is particularly prominent in squirrel monkey, extending for 2-3 mm from an injection. In both layers, these intrinsic connections are demonstrated by orthogradely and retrogradely transported HRP and seem to reflect a system of neurons with long horizontal axon collaterals, presumably with arborizations at regularly spaced intervals. The intrinsic connectional lattice in layers 2 and 3 resembles the repetitive array of cytochrome oxidase activity in these layers; but despite similarities of dimension and pattern, the two systems do not appear identical. In primate, as previously described in tree shrews (Rockland et al., '82), the HRP-labeled anatomical connections resemble the pattern of 2-deoxyglucose accumulation resulting from stimulation with oriented lines, although the functional importance of these connections remains obscure.

Animals↗

Afferent and efferent connections of cerebellar lobe C3 of the mormyrid fish Gnathonemus petersi: an HRP study.

The present paper is devoted to the extrinsic connections of lobe C3 of the highly differentiated corpus cerebelli of the electric fish Gnathonemus petersi. For this purpose, HRP injections or gels were placed in distinct parts of lobe C3 or its peduncle, in the pretectal region, and in the eye. Moreover, the presence of serotonin and tyrosine-hydroxylase was studied with immunohistochemical methods. The afferent connections of the rostral and caudal part of lobe C3 appear to differ considerably. Although both parts receive comparable projections from two pretectal nuclei (termed nucleus geniculatus and dorsal anterior pretectal nucleus) and the inferior olive, they receive projections from different parts of the nucleus lateralis valvulae, a large cell mass in the midbrain tegmentum, composed of small, tightly packed neurons. The caudal part of lobe C3 receives a projection from the most rostromedial cap of cells of this nucleus, whereas the rostral cap of lobe C3 receives efferents from the neighboring, more caudolateral, zone of cells of the nucleus lateralis valvulae. The caudal part of lobe C3, but not its rostral part, receives an additional projection from a nucleus in the isthmus region, termed nucleus Q. This nucleus sends a collateral projection to the torus longitudinalis. The efferents of both parts of lobe C3 project to slightly different parts of the midbrain tegmentum and the nucleus reticularis superior, and originate at least partly from eurydendroid cells. None of the nuclei and fiber tracts labeled could be shown to contain serotonin or catecholamines. The connections of lobe C3, as revealed by the present study, are compared with those of other parts of the mormyrid cerebellum and with those of the corpus cerebelli of other teleosts, with emphasis on the homology and functional significance of pretectocerebellar connections, the topical order in the cerebellar projections of the nucleus lateralis valvulae, and the relations between the cerebellum and torus longitudinalis. Comparison of the cerebellar connections in different teleostean species suggests that the strong development and the considerable differentiation of the cerebellum of mormyrids are related to at least two types of changes in the extrinsic connections, i.e.: a redistribution or parcelling of connections and the development of connections specific for mormyrids.

Afferent Pathways↗

Cortical connections of electrophysiologically and architectonically defined subdivisions of auditory cortex in squirrels.

Multiunit recordings with microelectrodes were used to identify and delimit subdivision of auditory cortex in squirrels. In the same animals, cortical connections of subdivisions of auditory cortex were determined by placing injections of the tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) into electrophysiologically defined locations. The electrophysiological results and patterns of connections were later related to myeloarchitectonic distinctions in brain sections cut parallel to the surface of the artificially flattened cortex. As previously described (Merzenich et al.: J. Comp. Neurol. 166:387-402, '76), a primary auditory field, A-I, was characterized by (1) neurons narrowly tuned to tone frequency; (2) a tonotopic map with high frequencies, which represented caudal to low frequencies; and (3) dense myelination. A-I was reciprocally connected with a rostral field, R, a parietal ventral somatosensory representation, PV, cortex ventral to A-I, and other nearby regions of cortex of the same hemisphere. Callosal connections of A-I were with A-I, R, and two or more other regions of temporal cortex. The less densely myelinated rostral field, R, also had neurons that were frequency tuned, but the neurons were often less securely driven. R appeared to have a tonotopic organization that roughly mirrored that of A-I. Ipsilateral connections of R included A-I, PV, and cortex ventral and caudal to R. Callosal connections were with R, A-I, PV, and cortex ventral and caudal to R. Callosal connections were with R, A-I, PV, and other locations in temporal cortex. Cortex in caudal PV, ventral to A-I, and ventral to R was responsive to auditory stimuli, but responses to pure tones were weak and inconsistent, and habituation to a repeated stimulus was rapid. The cortex responsive to auditory stimuli included some but not all of the cortex connected with A-I and R. The results lead to the conclusion that auditory cortex of squirrels contains at least two tonotopically organized fields, possibly as many as five or more auditory fields, and at least two auditory-somatosensory fields.

Animals↗

Intrinsic connections of rat primary visual cortex: laminar organization of axonal projections.

The organization of local projections within the rat primary visual cortex (area 17) was investigated by tracing fibers with HRP in in vitro brain slices. The projections from different layers showed distinct laminar patterns. Layer 4 made a strong, topographically precise, projection to lower layer 2/3; weaker projections extended laterally and terminated diffusely in layer 2/3 but also ran vertically to layers 5 and 6. The connections of lower and upper layer 2/3 were reciprocal and point-to-point. Within layer 2/3, a large number of fibers ran horizontally and terminated at variable distances from the injection site without making terminal clusters. The main output from layer 2/3 was to layer 5. The most prominent projections from the upper half of layer 5 were to layers 2/3 and 6; lower layer 5, in contrast, made wide-ranging, clustered projections to layer 1, the bottom of layer 2/3, and the top of layers 4 and 5. The patches were 130-160 micron wide and spaced apart by 230-260 micron. The main projection that arose from the superficial layer 6 terminated in layer 4 above the injection site. In contrast, lower layer 6 made clustered projections to the layer 3/4 border, extending up to 2 mm in the coronal plane. The patches were 190-220 micron wide and spaced apart by 320-390 micron. Additional projections went to the layer 5/6 border and layers 1 and 2. These results indicate that geniculocortical input is processed through interlaminar connections that are topographically precise, widespread, or patchy. These connectivity patterns suggest a role for these connections in the transformation of functional maps between layers; focused projections preserve the architecture of the layers of origin, and diverging or patchy projections rearrange this organization and form new maps in the target layers (Lund: Annu. Rev. Neurosci. 11:253-288, '88). However, only a few interlaminar connections show one of these patterns in isolation, making it difficult to assign a single function to a particular connection. We, therefore, tentatively conclude that projections terminating in layers 1-4, with the possible exception of the connection between upper layer 6 and layer 4, transform functional maps. In contrast, the topographically precise projections from upper to lower layers preserve functional maps. The specific role of these connections in the construction of receptive field properties, however, is not known.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ipsilateral cortical connections of granular frontal cortex in the strepsirhine primate Galago, with comparative comments on anthropoid primates.

Modern studies of granular frontal cortex (GFC) in large-brained, anthropoid primates, such as Macaca, indicate that this region is comprised of many areal subdivisions. These areas vary in their architectonic appearance and each has a distinctive, diverse set of corticocortical connections. The great extent of the GFC region in anthropoids, and its high degree of areal parcellation, suggest that some GFC areas may be specializations of anthropoids, not found in other mammals. To investigate this possibility, we studied the corticocortical connections of GFC in the relatively small-brained, strepsirhine primate Galago, with a series of eight tracer injections in the frontal cortex, and an additional eight injections of parietal and temporal cortex. Tracers used were wheat-germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids. Our results indicate that Galago GFC has strong, reciprocal connections with the parietal area-7 complex and with higher-order temporal areas; there are additional connections with extrastriate visual cortex, parahippocampal, and cingulate areas, and frontal cortex. Thus GFC has an extremely diverse array of cortical connections in Galago, as in Macaca. However, we also found that the pattern of parietofrontal connections is simpler in Galago than in Macaca. Specifically, parietal areas project to fewer discrete zones within the GFC of Galago, consistent with the view that these animals have fewer GFC areas than Macaca. In addition, Galago GFC possesses connections that specifically resemble those of Macaca arcuate cortex, but lacks connectional patterns that are characteristic of principalis cortex. These results are in accord with our previous architectonic studies, which indicated that Galago does not possess homologues of principalis areas. We conclude that the arcuate areas are common elements of primate GFC organization, while the areas located within and adjacent to the principal sulcus are anthropoid specializations.

Animals↗

Cytoarchitecture and intrafrontal connections of the frontal cortex of the brain of the hamadryas baboon (Papio hamadryas).

A study was made of the cytoarchitecture of the lateral and medial frontal cortex in the hamadryas baboon (Papio hamadryas). The frontal cortico-cortical connections of areas 46, 8, 6, and 4 were investigated by injection of wheat-germ agglutinine conjugated to horseradish peroxiase (WGA-HRP) into different regions of areas 46, 8, and 6. The lateral region of the frontal lobe of the baboon consists of broad areas of motor (area 4), premotor (area 6), and the dorsolateral prefrontal cortex, each of which is further divided into subdivisions with distinct cytoarchitectural features: areas 4a, 4b, 4c; 6 a alpha, 6a beta, 6a gamma, and 6b beta; 8A and 8B; 45; 46 and 46ps; 9; 10; and 12. Although the frontal cortex of the baboon brain exhibits the same basic cytoarchitectural features as the frontal corticies of the cercopithecus (campbelli?) (Vogt and Vogt, '19) or the macaque (Walker, '40; Barbas and Pandya, '87, '89), the baboon frontal cortex is very different from that of the macaque and cercopithecus in terms of cytoarchitecture: (1) the baboon frontal cortex has an additional area, termed here "6a gamma", within area 6, which has cytoarchitectural characteristics that are intermediate between those of areas 6 and 8; (2) the aggregation of giant pyramidal cells (greater than 50 microns in diameter) is found only in area 4a in the baboon, whereas such aggregates are found in areas 4a and 4b and, occasionally, in area 4c in the macaque; and (3) area 46 of the prefrontal cortex of the baboon can be subdivided into the cortex that surrounds the principal sulcus (area 46) and the upper and lower banks of the principal sulcus (area 46ps). Retrogradely WGA-HRP labeled cells and anterogradely WGA-HRP labeled terminals coexisted in the frontal cortex in a columnar fashion, indicative of a reciprocity among the connections. The frontal cortico-cortical connections of areas 46, 8, 6, and 4 in the hamadryas baboon were organized as follows: (1) areas 46, 8, and 6 were connected to one another, (2) area 4 was connected only to area 6, and (3) these connections showed a gross ventrodorsal topography: the ventral regions of each of areas 46, 8, and 6 were connected more strongly to the ventral than the dorsal regions of the other areas; the dorsal regions of each of areas 46, 8, and 6 were connected more strongly to the dorsal than the ventral regions of the other areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The dorsomedial visual area of owl monkeys: connections, myeloarchitecture, and homologies in other primates.

Cortical connections of the dorsomedial visual area (DM) of owl monkeys were revealed with injections of the bidirectional tracer, wheatgerm agglutinin conjugated with horseradish peroxidase (WGA-HRP), or the retrograde fluorescent tracer, diamidino yellow. Microelectrode recordings in two cases identified DM as a systematic representation of the visual hemifield in a densely myelinated rectangle of cortex just rostral to the dorsomedial portion of the second visual area (V-II, or area 18). Cortex was flattened and cut parallel to the surface in all cases so that the myeloarchitectonic borders of DM and other areas such as the primary visual area (V-I or area 17), V-II or area 18, and the middle temporal visual area (MT) could be readily determined, and the surface view patterns of connections could be directly appreciated. The ipsilateral pattern of connections of DM were dense and visuotopically congruent with area 17, area 18, and MT, and moderate to dense connections were with the medial visual area (M), the rostral division of the dorsolateral visual area, the dorsointermediate area, the ventral posterior area, the caudal division of inferotemporal cortex (ITc), the ventral posterior parietal area, and visuomotor cortex of the frontal lobe. The connections of DM were concentrated in the cytochrome oxidase (CO)-dense blobs of area 17, the CO-dense bands of area 18, and the CO-dense regions of MT. Callosal connections of DM were with matched locations in DM in the opposite hemisphere, and with VPP. The ipsilateral connections of DM with area 17 were confirmed by injecting WGA-HRP into area 17 in one owl monkey. In addition to labelled cells and terminals in area 18 and MT, bidirectionally transported tracer was also apparent in DM. Evidence for the existence of DM in other primates was obtained by injecting area 17 and examining the areal patterns of connections and myeloarchitecture in three species of Old World monkeys, two additional species of New World monkeys, and prosimian galagos. In all of these primates, one of three major targets of area 17 was a densely myelinated zone of cortex just rostral to dorsomedial area 18, in the location of DM in owl monkeys. Thus, it seems likely that DM is a visual area common to all primates.

Animals↗