Organization of horizontal axons in the inferior temporal cortex and primary visual cortex of the macaque monkey

We investigated the organization of horizontal connections at two distinct hierarchical levels in the ventral visual cortical pathway of the monkey, the inferior temporal (TE) and primary visual (V1) cortices. After injections of anterograde tracers into layers 2 and 3, clusters of terminals ('patches') of labeled horizontal collaterals in TE appeared at various distances up to 8 mm from the injection site, while in V1 clear patches were distributed only within 2 mm. The size and spacing of these patches in TE were larger and more irregular than those observed in V1. The labeling intensity of patches in V1 declined sharply with distance from the injection site. This tendency was less obvious in TE; a number of densely labeled patches existed at distant sites beyond weakly labeled patches. While injections into both areas resulted in an elongated pattern of patches, the anisotropy was greater in TE than in V1 for injections of a similar size. Dual tracer injections and larger-sized injections further revealed that the adjacent sites in TE had spatially distinct horizontal projections, compared to those in V1. These area-specific characteristics of the horizontal connections may contribute to the differences in visual information processing of TE and V1.     

Spacing of cytochrome oxidase blobs in visual cortex of normal and strabismic monkeys

Some models of visual cortical development are based on the assumption that the tangential organization of V1 is not determined prior to visual experience. In these models, correlated binocular activity is a key element in the formation of visual cortical columns, and when the degree of interocular correlation is reduced the models predict an increase in column spacing. To examine this prediction we measured the spacing of columns, as defined by cytochrome oxidase (CO) blobs, in the visual cortex of monkeys whose binocular vision was either normal or disrupted by a strabismus. The spatial distribution of blobs was examined in seven normal and five strabismic macaques. Tangential sections through the upper layers of the visual cortex were stained to reveal the two-dimensional (2D) pattern of CO blobs. Each blob was localized and their center-to-center spacing, packing arrangement and density were calculated using 2D nearest-neighbor spatial analyses. The mean center-to-center spacing of blobs (590 microm for normally reared and 598 microm for strabismic macaques) and the mean density of blobs (3.67 blobs/mm2 for normally reared and 3.45 blobs/mm2 for strabismic macaques) were not significantly different. In addition, the 2D packing arrangement of the blobs was not affected by strabismus. While it is clear that neural activity plays a key role in the elaboration and refinement of ocular dominance cortical modules, we conclude that it does not determine the spatial period of the pattern of CO blobs. This suggests that aspects of the neural circuitry underlying the columnar architecture of the visual cortex are established prenatally and its fundamental periodicity is not modifiable by experience.      

Laminar patterns of local excitatory input to layer 5 neurons in macaque primary visual cortex

Layer 5 neurons in primary visual cortex make putative reciprocal feedback connections to the superficial layers. To test this hypothesis, we employed scanning laser photostimulation combined with intracellular dye injection to examine local functional excitatory inputs to and axonal projections from individual layer 5 neurons in brain slices from monkey V1. In contrast with previous studies of other V1 neurons, layer 5 neurons received significant input from nearly all of the cortical layers, suggesting individual layer 5 cells integrate information from a broad range of input sources. Nevertheless relative strengths of laminar inputs varied across neurons. Cluster analysis of relative strength of laminar inputs to individual layer 5 neurons revealed four discrete clusters representing recurring input patterns; each cluster included both excitatory and inhibitory neurons. Twenty-five of 40 layer 5 neurons fell into two clusters, both characterized by very strong input from superficial layers. These input patterns are consistent with layer 5 neurons providing feedback to superficial layers. The remaining 15 neurons received stronger input from deep layers. Differences in input from layer 4Calpha versus 4Cbeta also suggest specific associations of the magnocellular and parvocellular visual pathways, with populations receiving stronger input from deep versus superficial cortical layers.     

Organization of intrinsic connections in owl monkey area MT

Area MT (middle temporal) is a well-defined visual representation common to all primates, which shows a clear selectivity to the analysis of visual motion. In the present study we examined the architecture of the intrinsic connections in area MT in an attempt to reveal its organizing principles and its potential relationship to the functional domains in area MT. Intrinsic connections were studied by placing small injections of the tracer biocytin in area MT of seven adult owl monkeys (Aotus nancymae). The injections were targeted at well-defined orientation domains revealed using optical imaging of intrinsic signals. The distribution of axons labeled by these injections was related both to the cytochrome oxidase histochemistry and to the layout of functional domains in area MT and surrounding tissue. Tracer injections in the superficial layers of area MT produced a complex network of extrinsic and intrinsic axonal connections. Clear instances of extrinsic connections were observed between area MT proper and the MT crescent situated postero-medially to it. The intrinsic connections were laterally spread and organized in patch-like clusters with an average distance from injection center to the furthest patch of 1.8 +/- 0.55 mm (+/-SD, n = 9). The overall axonal distribution tended to be anisotropic, i.e. the patches were distributed within an elongated ellipse [average anisotropy ratio: 1.86 +/- 0.66 (+/-SD)] and were asymmetrically distributed about either side of the injection site [average asymmetry ratio: 2.3 +/- 0.7 (+/-SD)]. Finally, there was a tendency for the intrinsic connections to connect to functional domains of similar orientation preference in area MT. However, this tendency varied substantially between individual cases. The highly specific nature of MT lateral connections puts clear constraints on models of surround influences in the receptive fields of MT neurons.      

Non-uniformity of neocortex: areal heterogeneity of NADPH-diaphorase reactive neurons in adult macaque monkeys

We have examined the distribution of cortical neurons in adult monkey cortex which stain for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), an enzyme which is involved in the synthesis of nitric oxide. In order to compare distributions across areas we employed a cortical unit defined as the radial column, which refers to the volume of cortex below 1 mm(2) of cortical surface. Numbers of labeled neurons per radial column generate areal density measurements either for the full thickness of the cortex or for individual layers. Measurements were made in six cortical regions (areas V1, V2, STS, auditory cortex, area 4 and area 6). NADPH-d stains nonpyramidal neurons which can be divided into two major groups. Type 1 neurons have large soma diameters, stain densely for NADPH-d and show few morphological variations both within and across areas. Type 2 neurons have small somata and short processes, and can be subdivided on the basis of soma size into dense and light staining categories. Both subcategories of type 2 neurons show significant areal variations in size. In each cortical area the majority of type 1 neurons are located in the white matter. Areal densities of type 1 neurons are minimal in areas V1 and V2, and twice as dense in the frontal cortex. Pairwise comparisons of areal densities among the six areas examined show that in a radial column throughout the full thickness of cortex, areas differ significantly from each other in 12/15 comparisons. Consideration of individual layers shows significant differences in 13/15 comparisons. Type 2 neurons are exclusively located in the cortical gray matter, and in all areas are considerably more numerous than type 1 neurons. Area V1 is unique it that it has up to three times the areal density found in any other cortical area. With reference to published laminar cell density counts our results show that the percentage of labeled NADPH-d neurons in individual layers of area V1 are significantly higher than in the other areas. The laminar distributions of type 1 and type 2 neurons show that each area has a unique profile of NADPH-d expression. The modular or columnar organization of the cortex, also referred to as the radial column hypothesis, is important for understanding both the development and function of the cortex. The present results show that radial columns in individual cortical areas possess distinctive patterns of NADPH-d expression. This important degree of areal heterogeneity of NADPH-d neurons has far reaching implications for both the development and functions of neocortical areas.     

Catecholaminergic innervation of pyramidal neurons in the human temporal cortex

In the human neocortex, catecholaminergic connections modulate the excitatory inputs of pyramidal neurons and are involved in higher cognitive functions. Catecholaminergic fibers form a dense network in which it is difficult to distinguish whether or not target specificity exists. In order to shed some light on this issue, we set out to quantify the catecholaminergic innervation of pyramidal cells in different layers of the human temporal cortex (II, IIIa, IIIb, V and VI). For this purpose, pyramidal cells were labeled in human cortical tissue by injecting them with Lucifer Yellow, and then performed immunocytochemistry for the rate limiting catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to visualize catecholaminergic fibers in the same sections. Injected cells were reconstructed in three dimensions and appositions were quantified (n = 1503) in serial confocal microscopy images of each injected cell (n = 71). We found TH-immunoreactive appositions (TH-ir) in all the pyramidal cells analyzed, in both the apical and basal dendritic regions. In general, the density of TH-ir apposition was greater in layers II, V and VI than in layers IIIa and IIIb. Furthermore, TH-ir appositions showed a regular distribution in almost all dendritic compartments of the apical and basal dendritic arbors across all layers. Hence, it appears that all pyramidal neurons in the human neocortex receive catecholaminergic afferents in a rather regular pattern, independent of the layer in which they are located. Since pyramidal cells located in different layers are involved in different intrinsic and extrinsic circuits, these results suggest that catecholaminergic afferents may modify the function of a larger variety of circuits than previously thought. Thus, this aspect of human cortical organization is likely to have important implications in cortical function.     

Efferent and afferent connections of mouse sensory-motor cortex following cholinergic deafferentation at birth.

The present study investigates the effect of cholinergic basal forebrain lesions at birth on cortical connectivity in adulthood. We have previously shown that such neonatal lesions result in extensive cortical cholinergic deafferentation during early postnatal development, which is accompanied by abnormal morphogenesis of cortical cytoarchitecture (H?hmann at al., 1988). Here, we have used WGA-HRP to label anterogradely and retrogradely afferent and efferent projections of dorsal neocortex. Our results show an altered projection pattern from dorsal thalamus to layer IV of sensory-motor cortex following lesions among the cholinergic basal forebrain neurons (nBM), while corticothalamic projections from layer VI appear normal. In addition, corticofugal projections from layer V, labeled by striatal injection, appear to be expanded following the lesion. This indicates that cortical layers undergoing differentiation after the newborn nBM lesion present with long-term abnormalities in connectivity. The present results are compatible with the hypothesis that cholinergic afferents are instrumental in the regulation of cortical morphogenesis. Furthermore, our data show that ontogenetic disturbances can lead to structural abnormalities that persist long after the initial deficiency has abated. We discuss the significance of these results in relationship to human neurological disorders.     

Anatomical Evidence for MT and Additional Cortical Visual Areas in Humans

We stained human visual cortex for myelin. cytochrome oxidase,and the monoclonal antibody CAT-301 in an attempt to demonstrateand map MT (V5) and other visual cortical areas in humans. Bothflattened and unflattened cortical tissue was examined. A likelycandidate for area MT (V5), which we refer to as MT was demonstratedusing all three stains. Myelin and CAT-301 labels for MT weredemonstrated to be coincident by comparing results from thetwo stains in adjacent sections. In all three stains, MT wasan oval area approximately 1.2 x 2.0 cm. located 5–6 cmanterior and dorsal to the foveal V1–V2 border. The positionand size of MT as defined by the present anatomy are consistentwith MT (V5) as defined by functional measures in humans. Inaddition, flattened cortical tissue stained for cytochrome oxidaserevealed a distinctive staining topography in several corticalareas, including areas V1, V2, MT, PX, and VX. Similar studiesin flattened cortex of macaque and green monkeys demonstrateddistinctive dark cytochrome oxidase staining in MT, PX, MTc,and V3.     

Relation between Patterns of Intrinsic Lateral Connectivity, Ocular Dominance, and Cytochrome Oxidase-Reactive Regions in Macaque Monkey Striate Cortex

To help understand the role of long-range, clustered lateralconnections in the superficial layers of macaque striate cortex(area V1), we have examined the relationship of the patternsof intrinsic connections to cytochrome oxidase (CO) blobs, interblobs,and ocular dominance (OD) bands, using biocytin based neuroanatomicaltracing, CO histochemistry, and optical imaging. Microinjectionsof biocytin in layer 3 resulted in an asymmetric field (averageanisotropy of 1.8; maximum spread—3.7 mm) of labeled axonterminal clusters in layers 1–3, with the longer axisof the label spread oriented orthogonal to the rows of blobsand imaged OD stripes, parallel to the V1/V2 border. These labeledterminal patches (n = 186) from either blob or interblob injections(n = 20) revealed a 71% (132 out of 186) commitment of patchesto the same compartment as the injection site; 11% (20 out of186) to the opposite compartment, and 18% (34 out of 186) toborders of blob-interblob compartments, indicating that theconnectivity pattern is not strictly blob to blob, or interblobto interblob (p < 0.005; $$$²) In injections placed withinsingle OD domains (n = 11), 54% of the resulting labeled terminalpatches (43 out of 79) fell into the same OD territories asthe injection sites, 28% (22 out of 79) into the opposite ODregions, and 18% (14 out of 79) on borders, showing some connectionalbias toward same-eye compartments (p < 0.02; ANOVA). Individualinjection cases, however, varied in the degree (50–100%for CO patterns, 22–100% for 0D patterns) to which theyshowed same-compartment connectivity. These results reveal thatwhile connectivity between similar compartments predominates(e.g., blob to blob, right eye column to right eye column),interactions do occur between functionally different regions.     

Weight consistency specifies regularities of macaque cortical networks

To what extent cortical pathways show significant weight differences and whether these differences are consistent across animals (thereby comprising robust connectivity profiles) is an important and unresolved neuroanatomical issue. Here we report a quantitative retrograde tracer analysis in the cynomolgus macaque monkey of the weight consistency of the afferents of cortical areas across brains via calculation of a weight index (fraction of labeled neurons, FLN). Injection in 8 cortical areas (3 occipital plus 5 in the other lobes) revealed a consistent pattern: small subcortical input (1.3% cumulative FLN), high local intrinsic connectivity (80% FLN), high-input form neighboring areas (15% cumulative FLN), and weak long-range corticocortical connectivity (3% cumulative FLN). Corticocortical FLN values of projections to areas V1, V2, and V4 showed heavy-tailed, lognormal distributions spanning 5 orders of magnitude that were consistent, demonstrating significant connectivity profiles. These results indicate that 1) connection weight heterogeneity plays an important role in determining cortical network specificity, 2) high investment in local projections highlights the importance of local processing, and 3) transmission of information across multiple hierarchy levels mainly involves pathways having low FLN values.     

Laminar specificity of intrinsic connections in Broca's area

Broca's area and its right hemisphere homologue comprise 2 cytoarchitectonic subdivisions, FDgamma and FCBm of von Economo C and Koskinas GN (1925, Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. Vienna/Berlin [Germany]: Springer). We report here on intrinsic connections within these areas, as revealed with biotinylated dextran amine and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate tracing in postmortem human brains. Injections limited to supragranular layers revealed a complex intrinsic network of horizontal connections within layers II and III spreading over several millimeters and to a lesser extent within layers IV, V, and VI. Ninety percent of the retrogradely labeled neurons (n = 734) were in supragranular layers, 4% in layer IV, and 6% in infragranular layers; most were pyramids and tended to be grouped into clusters of approximately 500 microm in diameter. Injections involving layer IV revealed extended horizontal connections within layers I-IV (up to 3.7 mm) and to a lesser extent in layers V and VI. Injections limited to the infragranular layers revealed horizontal connections mainly limited to these layers. Thus, intrinsic connections within Broca's area display a strong laminar specificity. This pattern is very similar in areas FDgamma and FCBm and in the 2 hemispheres.     

Coexistence of widespread clones and large radial clones in early embryonic ferret cortex.

Cell lineage analysis in rodents has shown that the cerebral cortex is formed from both widespread and large radial clustered clones representing partly distinct lineages and producing differing cell types. Since previous cell lineage analysis of the ferret cortex using retroviral libraries showed that most neurons labeled at E33-E35 formed widespread clones, we determined whether clones labeled earlier in neurogenesis showed a greater tendency to form coherent radial clones. Clones labeled at E27-E29 occasionally consisted of widespread multineuron clones (13% of PCR-defined clones), but commonly consisted of small clusters of two to four neurons (65%). Moreover, 6/21 hemispheres contained a single, much larger (6-150 cells) radial cluster. Although large clusters were observed in 28% of experiments, they contained many neurons, accounting for 38% of retrovirally labeled cells. The large clusters showed at most few widely scattered sibling cells, either by histological analysis or by PCR analysis, suggesting that radial and widespread clones coexist but are lineally separate at early stages of corticogenesis. Coexistence of large radial and widespread neuronal clones appears to be an evolutionarily conserved mechanism for cortical neurogenesis.     

Quantitative aspects of corticocortical connections: a tracer study in the mouse

This study provides neuroanatomical data relevant to models and simulations of the propagation of activity over the cortex. We administered small injections of the anterograde tracer biotinylated dextran amine to various regions of the mouse cortex (1 per animal). Two-dimensional reconstructions of the cortical surface were made, showing the distribution, size, and density of the terminal fields. Within the injected hemisphere, the largest part of the terminal field always surrounded the injection site and extended over neighboring areas. On average, axons from injection sites of 相似文献   

Regional, laminar, and cellular distribution of immunoreactivity for ER alpha and ER beta in the cerebral cortex of hormonally intact, adult male and female rats.

Behavioral, biochemical and anatomical studies suggest that estrogen stimulates structure and/or function in the adult cerebral cortex. The studies presented here used immunocytochemistry to map the alpha and beta isoforms of intracellular estrogen receptors (ER alpha, ER beta) in major subdivisions of adult rat cortex to identify potential sites for relevant receptor-mediated hormone actions. These studies revealed that immunoreactivity for ER alpha (ER alpha-IR) and ER beta (ER beta-IR) was present in most cortical areas, was associated exclusively with neurons, and was similar in males and females. Each receptor isoform also had its own unique distribution with respect to cortical regions, layers, and cells. In sensorimotor areas, for example, ER beta-IR was more prominent than ER alpha-IR, and was concentrated in layer V neurons that were immunoreactive for parvalbumin. In contrast, ER alpha-IR was scattered among parvalbumin-immunonegative cells in layers II/III and V/VI. Likewise, in entorhinal cortex, ER beta-IR was present in calbindin-containing cells in layers III-VI, while ER alpha-IR was restricted to small numbers of calbindin-negative neurons in infragranular layers. In sum, ER beta-IR and ER alpha-IR were differentially distributed both with respect to cortical compartments and with respect to each other. Accordingly, estrogen activation at these two sites may be anticipated to impact disparate sets of cortical circuits, cells, and functions.     

Axon topography of layer IV spiny cells to orientation map in the cat primary visual cortex (area 18)

Our aim was to reveal the relationship between layer IV horizontal connections and the functional architecture of the cat primary visual cortex because these connections play important roles in the first cortical stage of visual signals integration. We investigated bouton distribution of spiny neurons over an orientation preference map using in vivo optical imaging, unit recordings, and single neuron reconstructions. The radial extent of reconstructed axons (14 star pyramidal and 9 spiny stellate cells) was ~1.5 mm. In the vicinity of the parent somata (<400 μm), boutons occupied chiefly iso-orientations, however, more distally, 7 cells projected preferentially to non-iso-orientations. Boutons of each cell were partitioned into 1-15 distinct clusters based on the mean-shift algorithm, of which 57 clusters preferred iso-orientations and 43 clusters preferred cross-orientations, each showing sharp orientation preference "tuning." However, unlike layer III/V pyramidal cells preferring chiefly iso-orientations, layer IV cells were engaged with broad orientations because each bouton cluster from the same cell could show different orientation preference. These results indicate that the circuitry of layer IV spiny cells is organized differently from that of iso-orientation dominant layer III/V cells and probably processes visual signals in a different manner from that of the superficial and deeper layers.     

The distribution of immunoreactivity for intracellular androgen receptors in the cerebral cortex of hormonally intact adult male and female rats: localization in pyramidal neurons making corticocortical connections

Gonadal hormones are known to broadly influence cortical information processing. Findings from this study in rats suggest that for androgens, this influence may include stimulation of underlying corticocortical connections. First, immunoreactivity for intracellular androgen receptors, while present in all regions and layers examined, was found to be particularly abundant in sensory and motor regions, and within these, within their major pyramidal cell layers, i.e. layers II/III and V/VI. Double labeling immunocytochemical studies for androgen receptors and for neuron-specific markers then confirmed that the majority of receptor-bearing cortical cells were pyramidal neurons. Finally, combined analyses of cortical receptor immunoreactivity and retrograde labeling produced by tracer injections made in specific subcortical (caudate, nucleus accumbens, superior colliculus, thalamus) areas yielded only isolated examples of receptor/tracer overlap. However, injections made within the cortex itself (sensory, motor, associational areas) retrogradely labeled cortical cells some 50% or more - especially within injected hemispheres, were receptor-immunoreactive. Thus, the regional, laminar, and cellular distributions of immunoreactivity in the rat cerebrum largely identify pyramidal neurons with connectional signatures aligning intracellular androgen receptors with the local, associational, and to a lesser degree, callosal circuits that interlink territories of the cortical mantle and play key roles in cortical information processing.     

Anatomical evidence for classical and extra-classical receptive field completion across the discontinuous horizontal meridian representation of primate area V2

In primates, a split of the horizontal meridian (HM) representation at the V2 rostral border divides this area into dorsal (V2d) and ventral (V2v) halves (representing lower and upper visual quadrants, respectively), causing retinotopically neighboring loci across the HM to be distant within V2. How is perceptual continuity maintained across this discontinuous HM representation? Injections of neuroanatomical tracers in marmoset V2d demonstrated that cells near the V2d rostral border can maintain retinotopic continuity within their classical and extra-classical receptive field (RF), by making both local and long-range intra- and interareal connections with ventral cortex representing the upper visual quadrant. V2d neurons located <0.9-1.3 mm from the V2d rostral border, whose RFs presumably do not cross the HM, make nonretinotopic horizontal connections with V2v neurons in the supra- and infragranular layers. V2d neurons located <0.6-0.9 mm from the border, whose RFs presumably cross the HM, in addition make retinotopic local connections with V2v neurons in layer 4. V2d neurons also make interareal connections with upper visual field regions of extrastriate cortex, but not of MT or MTc outside the foveal representation. Labeled connections in ventral cortex appear to represent the "missing" portion of the connectional fields in V2d across the HM. We conclude that connections between dorsal and ventral cortex can create visual field continuity within a second-order discontinuous visual topography.     

Corticocortical associative neurons expressing latexin: specific cortical connectivity formed in vivo and in vitro.

Latexin, a carboxypeptidase A inhibitor, is expressed in a subset of neurons in the infragranular layers of the lateral cortex in the rat. We here show that latexin-expressing neurons exhibit ultrastructural features common to cortical pyramidal neurons. We show in combined retrograde tracing and immunofluorescent experiments that latexin-expressing neurons contribute to specific corticocortical pathways. Thus, injections of the retrograde tracer fluorogold into either the primary somatosensory (SI) or the primary motor (MI) cortical area labeled many latexin-expressing neurons in the infragranular layers of the secondary somatosensory (SII) and visceral sensory (Vi) areas. In contrast, tracer injections involving the thalamus, striatum, or contralateral SII and Vi exclusively labeled latexin-nonexpressing neurons in both the SII and Vi. Finally, we show that the correct corticocortical projections can be formed in organotypic slice cultures in vitro from latexin-expressing neurons: when slices of developing SII were cocultured with those from the SI and the thalamus, latexin-immunoreactive neurons in the SII projected preferentially to their normal SI target. The specific connectivity formed in vivo and in vitro by this molecularly distinct neuronal population reveals its characteristic manner of cortical organization and provides a unique model system to analyze mechanisms underlying the formation of precise corticocortical pathways.