Cortical connections of areas V3 and VP of macaque monkey extrastriate visual cortex

The cortical connections of visual area 3 (V3) and the ventral posterior area (VP) in the macaque monkey were studied by using combinations of retrograde and anterograde tracers. Tracer injections were made into V3 or VP following electrophysiological recording in and near the target area. The pattern of ipsilateral cortical connections was analyzed in relation to the pattern of interhemispheric connections identified after transection of the corpus callosum. Both V3 and VP have major connections with areas V2, V3A, posterior intraparietal area (PIP), V4, middle temporal area (MT), medial superior temporal area (dorsal) (MSTd), and ventral intraparietal area (VIP). Their connections differ in several respects. Specifically, V3 has connections with areas V1 and V4 transitional area (V4t) that are absent for VP; VP has connections with areas ventral occipitotemporal area (VOT), dorsal prelunate area (DP), and visually responsive portion of temporal visual area F (VTF) that are absent or occur only rarely for V3. The laminar pattern of labeled terminals and retrogradely labeled cell bodies allowed assessment of the hierarchical relationships between areas V3 and VP and their various targets. Areas V1 and V2 are at a lower hierarchical level than V3 and VP; all of the remaining areas are at a higher level. V3 receives major inputs from layer 4B of V1, suggesting an association with the magnocellular-dominated processing stream and a role in routing magnocellular-dominated information along pathways leading to both parietal and temporal lobes. The convergence and divergence of pathways involving V3 and VP underscores the distributed nature of hierarchical processing in the visual system. J. Comp. Neurol. 379:21-47, 1997. © 1997 Wiley-Liss, Inc.     

Heterogeneity of extrastriate visual areas and multiple parietal areas in the macaque monkey

The definition of visual areas remains a key problem in the effort to elucidate cortical functions. Visual areas vary along a number of dimensions and are increasingly difficult to define according to traditional criteria at higher levels of the hierarchy. Three recently discovered areas in monkey parietal association cortex illustrate a new approach to this problem. Their definition depends on assessment of neuronal response properties in the alert, behaving animal combined with precise reconstruction of recording sites. This approach permits recognition of functionally distinct areas in the absence of retinotopic maps.     

Organization of the callosal connections of visual areas V1 and V2 in the macaque monkey

The interhemispheric efferent and afferent connections of the V1/V2 border have been examined in the adult macaque monkey with the tracers horseradish peroxidase and horseradish peroxidase conjugated to wheat germ agglutinin. The V1/V2 border was found to have reciprocal connections with the contralateral visual area V1, as well as with three other cortical sites situated in the posterior bank of the lunate sulcus, the anterior bank of the lunate sulcus, and the posterior bank of the superior temporal sulcus. Within V1, callosal projecting cells were found mainly in layer 4B with a few cells in layer 3. Anterograde labeled terminals were restricted to layers 2, 3, 4B, and 5. In extrastriate cortex, retrograde labeled cells were in layers 2 and 3 and only very rarely in infragranular layers. In the posterior bank of the lunate sulcus, labeled terminals were scattered throughout all cortical layers except layers 1 and 4. In the anterior bank of the lunate sulcus and in the superior temporal sulcus, anterograde labeled terminals were largely focused in layer 4. Callosal connections in all contralateral regions were organized in a columnar fashion. Columnar organization of callosal connections was more apparent for anterograde labeled terminals than for retrograde labeled neurons. In the posterior bank of the lunate sulcus, columns of callosal connections were superimposed on regions of high cytochrome activity. The tangential extent of callosal connections in V1 and V2 was found to be influenced by eccentricity in the visual field. Callosal connections were denser in the region of V1 subserving foveal visual field than in cortex representing the periphery. In V1 subserving the fovea, callosal connections extended up to 2 mm from the V1/V2 border and only up to 1 mm in more peripheral located cortex. In area V2 subserving the fovea, cortical connections extended up to 8 mm from the V1/V2 border and only up to 3 mm in peripheral cortex.     

Visual areas in lateral and ventral extrastriate cortices of the marmoset monkey

The representation of the visual field in visual areas of the dorsolateral, lateral, and ventral cortices was studied by means of extracellular recordings and fluorescent tracer injections in anaesthetised marmoset monkeys. Two areas, forming mirror-symmetrical representations of the contralateral visual field, were found rostral to the second visual area (V2). These were termed the ventrolateral posterior (VLP) and the ventrolateral anterior (VLA) areas. In both areas, the representation of the lower quadrant is located dorsally, between the foveal representation of V2 and the middle temporal crescent (MTc), whereas the representation of the upper quadrant is located ventrally, in the supratentorial cortex. A representation of the vertical meridian forms the common border of areas VLP and VLA, whereas the horizontal meridian is represented both at the caudal border of area VLP (with V2) and at the rostral border of area VLA (with multiple extrastriate areas). The foveal representations of areas VLP and VLA are continuous with that of V2, being located at the lateral edge of the hemisphere. The topographic and laminar patterns of projections from dorsolateral and ventral cortices to the primary (V1) and dorsomedial (DM) visual areas both support the present definition of the borders of areas VLP and VLA. These results argue against a separation between dorsolateral and ventral extrastriate areas and provide clues for the likely homologies between extrastriate areas of different species.     

The relationship between V6 and PO in macaque extrastriate cortex

The cerebral cortex of three macaque monkeys, electrophysiologically studied in chronic preparations in order to recognize functionally the medial parieto-occipital area V6, was reconstructed using the software CARET. Locations of cells recorded from area V6 (n = 553) and from neighbouring cortical areas V2/V3 and V6A (n = 1341) were displayed on surface-based reconstructions of individual brains, and on a surface-based atlas of the macaque cerebral cortex. Results show that area V6 occupies the ventral part and fundus of the parieto-occipital sulcus, as well as the ventral part of the precuneate cortex. V6 borders areas V2/V3 posteriorly and laterally, and area V6A anteriorly. The visualization of individual cases on a common template (atlas), and the use of atlas datasets, allowed us to compare data coming from different individuals and different laboratories. In particular, a comparison of the location and extent of the medial parieto-occipital areas V6 and PO indicates that area PO occupies different locations according to different authors but in general includes parts of both areas V6 and V6A. We therefore suggest that the term V6 is a more appropriate designation of the visuotopically-organized area located on the anterior wall of the parieto-occipital sulcus.     

Functional implications of the anatomical organization of the callosal projections of visual areas V1 and V2 in the macaque monkey

The efferent and afferent connections of the V1/V2 border with the contralateral hemisphere have been examined using anatomical tracers. The V1/V2 border was found to exchange connections with the contralateral V2 area as well as a restricted strip of V1 lying adjacent to the V1/V2 border. Besides these homotopic projections, two heterotopic projections were found to V3/V3A and V5. Anterograde tracing of callosal connections showed that terminals in these heterotopic sites were focused in layer 4, the recipient layer of projections originating from the ipsilateral V1/V2 border. Bilateral injections of fluorescent dyes showed that these heterotopic targets of the V1/V2 border are connected to the homologous ipsilateral V1/V2 border region. The laminar location of callosal projecting neurons as well as their terminals were characteristic for each cortical region. The laminar pattern of callosal connectivity was found to differ markedly from that of associational visual pathways. Two principal hypotheses are suggested by these results. First, the fact that V1 in part is reciprocally callosally connected in all mammals supports the notion that this interhemispheric pathway completes long-range intrinsic cortical connections. Second, the convergence of inter- and intrahemispheric pathways could provide the anatomical basis for the modulation of the sensory processing within one hemisphere by ongoing activity in the contralateral hemisphere.     

Organization of callosal linkages in visual area V2 of macaque monkey

In visual area V2 of the macaque monkey callosal cells accumulate in finger-like bands that extend 7-8 mm from the V1/V2 border, or approximately half the width of area V2. The present study investigated whether or not callosal connections in area V2 link loci that are located at the same distance from the V1/V2 border in both hemispheres. We analyzed the patterns of retrograde labeling in V2 resulting from restricted injections of fluorescent tracers placed at different distances from the V1/V2 border in contralateral area V2. The results show that varying the distance of V2 tracer injections from the V1/V2 border led to a corresponding variation in the location of labeled callosal cells in contralateral V2. Injections into V2 placed on or close to the V1 border produced labeled cells that accumulated on or close to the V1 border in contralateral V2, whereas injections into V2 placed away from the V1 border produced labeled cells that accumulated mainly away from the V1 border. These results provide evidence that callosal fibers in V2 preferentially link loci that are located at similar distances from the V1/V2 border in both hemispheres. Relating this connectivity pattern to the topographic map of V2 suggests that callosal fibers link topographically mirror-symmetrical regions of V2, i.e., callosal fibers near the V1/V2 border interconnect areas representing visual fields on, or close to, the vertical meridian, whereas callosal connections from regions away from the V1/V2 border interconnect visuotopically mismatched visual fields that extend onto opposite hemifields.     

The projections from striate cortex (V1) to areas V2 and V3 in the macaque monkey: asymmetries, areal boundaries, and patchy connections

The organization of projections from V1 to areas V2 and V3 in the macaque monkey was studied with a combination of anatomical techniques, including lesions and tracer injections made in different portions of V1 and V2 in 20 experimental hemispheres. Our results indicate that dorsal V1 (representing the inferior contralateral visual quadrant) consistently projects in topographically organized fashion to V3 in the lunate and parietooccipital sulci as well as to the middle temporal area (MT) and dorsal V2. In contrast, ventral V1 (representing the superior contralateral quadrant) projects only to MT and ventral V2. A corresponding dorsoventral asymmetry in myeloarchitecture supports the idea that V3 is an area that is restricted to dorsal extrastriate cortex and lacks a complete representation of the visual field. The average surface area of myeloarchitectonically identified V3 was 89 mm2. Additional information was obtained concerning the laminar distribution of connections from V1 to V2 and V3, the patchiness of these projections, and the consistency of projections to other extrastriate areas, including V4 and V3A.     

Differential expression of muscarinic acetylcholine receptors across excitatory and inhibitory cells in visual cortical areas V1 and V2 of the macaque monkey

Cholinergic neuromodulation, a candidate mechanism for aspects of attention, is complex and is not well understood. Because structure constrains function, quantitative anatomy is an invaluable tool for reducing such a challenging problem. Our goal was to determine the extent to which m1 and m2 muscarinic acetylcholine receptors (mAChRs) are expressed by inhibitory vs. excitatory neurons in the early visual cortex. To this end, V1 and V2 of macaque monkeys were immunofluorescently labelled for gamma-aminobutyric acid (GABA) and either m1 or m2 mAChRs. Among the GABA-immunoreactive (ir) neurons, 61% in V1 and 63% in V2 were m1 AChR-ir, whereas 28% in V1 and 43% in V2 were m2 AChR-ir. In V1, both mAChRs were expressed by fewer than 10% of excitatory neurons. However, in V2, the population of mAChR-ir excitatory neurons was at least double that observed in V1. We also examined m1 and m2 AChR immunoreactivity in layers 2 and 3 of area V1 under the electron microscope and found evidence that GABAergic neurons localize mAChRs to the soma, whereas glutamatergic neurons expressed mAChRs more strongly in dendrites. Axon and terminal labelling was generally weak. These data represent the first quantitative anatomical study of m1 and m2 AChR expression in the cortex of any species. In addition, the increased expression in excitatory neurons across the V1/V2 border may provide a neural basis for the observation that attentional effects gain strength up through the visual pathway from area V1 through V2 to V4 and beyond.     

Pattern of extrastriate visual areas connecting reciprocally with striate cortex in the mouse

Several areas reciprocally connected to striate cortex were found in the extrastriate cortex of the mouse after small single injections of horseradish peroxidase into the striate cortex. By showing that the arrangement of these labeled extrastriate areas resembles closely the physiologic and anatomic subdivision of the extrastriate cortex reported previously in several rodent species, this study supports the hypothesis that there exists a common pattern of visual cortical organization in rodents.     

Demonstration of lack of dorsal lateral geniculate nucleus input to extrastriate areas MT and Visual 2 in the macaque monkey

Injections of wheat germ conjugated and normal horseradish peroxidase in the identifiable extrastriate cortical areas MT and Visual 2 of the macaque monkey, indicate that these areas do not receive an input from the dorsal lateral geniculate nucleus as do other regions of extrastriate visual cortex.     

Ventral visual cortex in humans: cytoarchitectonic mapping of two extrastriate areas

The extrastriate visual cortex forms a complex system enabling the analysis of visually presented objects. To gain deeper insight into the anatomical basis of this system, we cytoarchitectonically mapped the ventral occipital cortex lateral to BA 18/V2 in 10 human postmortem brains. The anatomical characterization of this part of the ventral stream was performed by examination of cell-body-stained histological sections using quantitative cytoarchitectonic analysis. First, the gray level index (GLI) was measured in the ventral occipital lobe. Cytoarchitectonic borders, i.e., significant changes in the cortical lamination pattern, were then identified using an observer-independent algorithm based on multivariate analysis of GLI profiles. Two distinct cytoarchitectonic areas (hOC3v, hOC4v) were characterized in the ventral extrastriate cortex lateral to BA 18/V2. Area hOC3v was found in the collateral sulcus. hOC4v was located in this sulcus and also covered the fusiform gyrus in more occipital sections. Topographically, these areas thus seem to represent the anatomical substrates of functionally defined areas, VP/V3v and V4/V4v. Following histological analysis, the delineated cytoarchitectonic areas were transferred to 3D reconstructions of the respective postmortem brains, which in turn were spatially normalized to the Montreal Neurological Institute reference space. A probabilistic map was generated for each area which describes how many brains had a representation of this area in a particular voxel. These maps can now be used to identify the anatomical correlates of functional activations observed in neuroimaging experiments to enable a more informed investigation into the many open questions regarding the organization of the human visual cortex.     

Reciprocal connections between the striate cortex and extrastriate cortical visual areas in the rat

Following injections of horseradish peroxidase (HRP) in the striate cortex of rats, a precise topographical correspondence between extrastriate cortical fields of anterograde and retrograde label was observed. The arrangement of these extrastriate labeled fields corresponds closely to the previously reported division of the peristriate cortex into multiple visual areas, suggesting that each of these areas is reciprocally connected to striate cortex. Cortical layers II–VI participate in this reciprocal connection.     

Sensitivity to horizontal and vertical disparity and orientation preference in areas V1 and V2 of the monkey

It has been suggested that cells are most sensitive to disparities along the axis orthogonal to their orientation preference. To test this assumption we studied the orientation preference of 73 cells sensitive to retinal disparity, 44 from V1 and 29 from V2. Orientation preference and disparity sensitivity were not related in tuned excitatory and tuned inhibitory cells. We found 18 near/far cells with orientation preference. Of these, 10 (56%) had a preferred orientation less than 30% away from the orthogonal to the disparity axis whereas the remaining eight cells (44%) exceeded this value. Our data suggests that the neural mechanisms for encoding retinal disparities present in dynamic random dot stereograms may not be related to the preferred orientation of the cell.     

Synaptic organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey

The primate amygdaloid complex projects to a number of visual cortices, including area V1, primary visual cortex, and area TE, a higher-order unimodal visual area involved in object recognition. We investigated the synaptic organization of these projections by injecting anterograde tracers into the amygdaloid complex of Macaca fascicularis monkeys and examining labeled boutons in areas TE and V1 using the electron microscope. The 256 boutons examined in area TE formed 263 synapses. Two hundred twenty-three (84%) of these were asymmetric synapses onto dendritic spines and 40 (15%) were asymmetric synapses onto dendritic shafts. Nine boutons (3.5%) formed double asymmetric synapses, generally on dendritic spines, and 2 (1%) of the boutons did not form a synapse. The 200 boutons examined in area V1 formed 211 synapses. One hundred eighty-nine (90%) were asymmetric synapses onto dendritic spines and 22 (10%) were asymmetric synapses onto dendritic shafts. Eleven boutons (5.5%) formed double synapses, usually with dendritic spines. We conclude from these observations that the amygdaloid complex provides an excitatory input to areas TE and V1 that primarily influences spiny, probably pyramidal, neurons in these cortices.     

The organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey

We examined the organization of amygdaloid projections to visual cortical areas TE and V1 by injecting anterograde tracers into the amygdaloid complex of Macaca fascicularis monkeys. The magnocellular and intermediate divisions of the basal nucleus of the amygdala gave rise to heavy projections to both superficial layers (border of I/II) and deep layers (V/VI) throughout the rostrocaudal extent of area TE. Although most of the injections led to heavier fiber and terminal labeling in the superficial layers of area TE, the most dorsal injections in the basal nucleus produced denser labeled fibers and terminals in the deep layers of area TE. Area V1 received projections primarily from the magnocellular division of the basal nucleus, and these terminated exclusively in the superficial layers. As in area TE, projections from the amygdala to area V1 were distributed throughout its rostrocaudal and transverse extents. Labeled axons demonstrated 11.67 varicosities/100 microm on average in the superficial layers of area TE and 8.74 varicosities/100 microm in the deep layers. In area V1 we observed 8.24 varicosities/100 microm. Using confocal microscopy, we determined that at least 55% of the tracer-labeled varicosities in areas TE and V1 colocalized synaptophysin, a marker of synaptic vesicles, indicating that they are probably synaptic boutons. Electron microscopic examination of a sample of these varicosities confirmed that labeled boutons formed synapses in areas TE and V1. These feedback-like projections from the amygdala have the potential of modulating key areas of the visual processing system.     

Stereoscopic mechanisms in monkey visual cortex: binocular correlation and disparity selectivity

The neural signals in visual cortex associated with positional disparity and contrast texture correlation of binocular images are the subject of this study. We have analyzed the effects of stereoscopically presented luminous bars and of dynamic random-dot patterns on the activity of single neurons in cortical visual areas V1, V2, and V3-V3A of the alert, visually trained rhesus macaque. The interpretation of the results and considerations of possible neural mechanisms led us to recognize 2 functional sets of stereoscopic neurons. (1) A set of neurons, tuned excitatory (T0) or tuned inhibitory (TI), which respond sharply to images of zero or near-zero disparity. Objects at or about the horopter drive the T0 neurons and suppress the TI, while objects nearer and farther have the opposite effects on each type, inhibition of the T0 and excitation of the TI. The activity of these neurons may provide, in a reciprocal way, the definition of the plane of fixation, and the basic reference for binocular single vision and depth discrimination. (2) A second set of neurons includes tuned excitatory at larger crossed or uncrossed disparities (TN/TF) and neurons with reciprocal excitatory and inhibitory disparity sensitivity with cross-over at the horopter (NE/FA). Binocularly uncorrelated image contrast drives these neurons to a maintained level of activity, which shifts, in response to correlated images, toward facilitation or suppression as a function of positional disparity. These neurons may operate in the neural processing leading to stereopsis, both coarse and fine, and also provide signals for the system controlling binocular vergence. These results indicate that cortical visual neurons are binocularly linked to respond to the relative position and contrast of the images over their receptive fields, and also that both these aspects of binocular stimulation may be utilized by the brain as a source of stereoscopic information.     

Neuronal activity in monkey visual areas V1, V2, V4, and TEO during fixation task

We analyzed 577 neurons recorded from visual areas V1, V2, V4, and the inferotemporal area (TEO) of macaque monkeys, which performed a visual fixation task and a spot-off-on (blink) test during the fixation period. Among these neurons, 35% were defined as task-related cells, because they gave responses at the task-start, fixation, or task-end periods but were unresponsive to the spot blink, which was physically identical to these stimuli. Blink-responsive cells accounted for 29% and task-unresponsive cells for 30% of the neurons. The task-related response was large and frequent in V4 (34%) and TEO (41%), but small and less frequent in V1 (31%) and V2 (27%). Other observations further demonstrated nonsensory activities in these areas: In some cells, response to the fixation spot was inhibitory, whereas light stimulation on the fovea was excitatory; some V1 and V2 cells had color-irrelevant responses, and some cells responded to the spot-off only when the monkey regarded it as a task-end cue.     

Binocular interaction and sensitivity to horizontal disparity in visual cortex in the awake monkey

We evaluated the binocular interaction and horizontal disparity sensitivity in neurons recorded from macaque visual cortex. Neurons from V1 of three awake Macaca mulatta monkeys were isolated by means of extracellular recording and tested for disparity sensitivity with dynamic random dot stereograms. Neurons sensitive to horizontal disparities were stimulated both monocularly and binocularly with flashing bars and their responses quantified. ANOVA and regression tests were used for data analysis. Sixty-six cells out of 185 (66/185, 36%) showed sensitivity to horizontal disparity. Disparity sensitive cells were grouped into near (25/66, 38%), tuned inhibitory (16/66, 24%), far (13/66, 20%) and tuned excitatory (12/66, 18%). Receptive fields of tuned cells were located more centrally in the visual field than those of near and far cells. The binocular interaction in tuned inhibitory cells increased linearly along with ocular unbalance. Most of tuned excitatory cells (10/12, 83%) showed facilitatory binocular interaction, characterized by a stronger response to binocular stimulation than to the stimulation of the dominant eye. On the contrary, most of tuned inhibitory cells (14/16, 88%) showed suppressory binocular interaction, characterized by a weaker response to binocular stimulation than to the stimulation of the dominant eye. Near and far cells showed both types of interaction in similar percentages. The binocular response showed a linear relationship with the sum of both monocular responses in tuned excitatory, tuned inhibitory and near cells, but not in far cells. Sensitivity to horizontal disparity may be a result of facilitatory and suppressive interactions between left and right inputs.     

A double-labeling investigation of the afferent connectivity to cortical areas V1 and V2 of the macaque monkey

The afferent connectivity of areas V1 and V2 was investigated using the fluorescent dyes fast blue and diamidino yellow. Simultaneous injection of each dye in retinotopically corresponding regions of these areas gave rise to two afferent populations of labeled neurons in subcortical and cortical structures which project to both areas. These two populations showed a variable degree of overlap in their spatial distribution. Neurons labeled by both dyes (double-labeled neurons) which, therefore, project to both areas, were found in substantial numbers in these overlap zones. When the injections were made in non-retinotopically corresponding regions in the two areas, both populations of labeled cells overlapped extensively in the cortex but not in subcortical structures, suggesting that the laws governing the topography of these two types of connections are different. In the cortex, the labeled neurons extended from the fundus of the lunate sulcus to the fundus of the superior temporal sulcus. A few labeled neurons were also found in the inferior temporal cortex and the parahippocampal gyrus. In all cortical regions, corticocortical neurons projecting to V1 and V2 were found in both supra- and infragranular layers, although double-labeled neurons were more numerous in infragranular layers. With increasing distance from V1 there was an increase in the proportion of neurons labeled in infragranular layers. The comparative strength of input to V1 and V2 was computed and was found to be higher to V2 in all cortical regions except the superior temporal sulcus which projected equally heavily to both areas. The superior temporal sulcus also stood out in that of all cortical regions it contained the highest proportion of double-labeled neurons. Single- and double-labeled neurons were found in a number of subcortical structures including the lateral geniculate nucleus, the inferior and lateral pulvinar, the intralaminar nuclei, the nucleus basalis of Meynert, and the amygdala. The pattern of labeling in the lateral pulvinar was in agreement with the suggestion that this structure has a complex topographical organization containing at least a dual representation of the visual field (Bender, D. B. (1981) J. Neurophysiol. 46: 672-693). In the pulvinar complex, densities of labeled neurons permitted evaluation of the strength of input to V1 and V2, the latter being the strongest. These results demonstrate that areas V1 and V2 share a vast amount of common input from the same cortical and subcortical structures and that a number of neurons project to both areas via branching axons.