Diversity and cell type specificity of local excitatory connections to neurons in layer 3B of monkey primary visual cortex

In the primary visual cortex of macaque monkeys, laminar and columnar axonal specificity are correlated with functional differences between locations. We describe evidence that embedded within this anatomical framework is finer specificity of functional connections. Photostimulation-based mapping of functional input to 31 layer 3B neurons revealed that input sources to individual cells were highly diverse. Although some input differences were correlated with neuronal anatomy, no 2 neurons received excitatory input from the same cortical layers. Thus, input diversity reveals far more cell types than does anatomical diversity. This implies relatively little functional redundancy; despite trends related to laminar or columnar position, pools of neurons contributing uniquely to visual processing are likely relatively small. These results also imply that similarities in the anatomy of circuits in different cortical areas or species may not indicate similar functional connectivity.     

The connectional organization of neural systems in the cat cerebral cortex

BACKGROUND: The mammalian brain consists of the cerebral cortical sheet, which is composed of many distinct areas, the cerebellar cortex, and many non-cortical nuclei. Powerful neuroanatomical techniques have revealed a large number of connections between these structures. The large number of brain structures and the very many connections between them form a strikingly complex network. The complexity of this network has made it difficult to understand how the central nervous system is organized. Recently, however, optimization analysis of an important subset of central nervous connections that occur between the different areas of the cerebral cortex has produced understandable and quantitative representations of the organization of cortical systems of the primate brain. RESULTS: Here we briefly report the extension of this approach to the cortical systems of the cat. There were four connectional clusters of cortical areas in the cat. These clusters of areas corresponded to the visual, auditory, and somato-motor systems, and to the frontal and limbic areas, which we call the fronto-limbic complex. All the major sensory systems were hierarchically organized, and their 'higher' stations were more closely associated with the fronto-limbic complex than were their 'lower' stations. CONCLUSIONS: Features of the organization of the cat brain, together with earlier primate results, suggest that there may be a common cortical plan in mammals. We suggest that this common plan may involve relatively discrete, hierarchically organized, cortical sensory systems and a topologically central fronto-limbic complex. Specific variations on this wiring plan may relate to evolutionary history and selection for particular ecological niches.     

Four concurrent feedforward and feedback networks with different roles in the visual cortical hierarchy

Visual stimuli evoke fast-evolving activity patterns that are distributed across multiple cortical areas. These areas are hierarchically structured, as indicated by their anatomical projections, but how large-scale feedforward and feedback streams are functionally organized in this system remains an important missing clue to understanding cortical processing. By analyzing visual evoked responses in laminar recordings from 6 cortical areas in awake mice, we uncovered a dominant feedforward network with scale-free interactions in the time domain. In addition, we established the simultaneous presence of a gamma band feedforward and 2 low frequency feedback networks, each with a distinct laminar functional connectivity profile, frequency spectrum, temporal dynamics, and functional hierarchy. We could identify distinct roles for each of these 4 processing streams, by leveraging stimulus contrast effects, analyzing receptive field (RF) convergency along functional interactions, and determining relationships to spiking activity. Our results support a dynamic dual counterstream view of hierarchical processing and provide new insight into how separate functional streams can simultaneously and dynamically support visual processes.

Visual stimuli evoke fast-evolving activity patterns that are distributed across multiple cortical areas, but how large-scale feedforward and feedback streams are functionally organized in this system remains unclear. Visual evoked responses in laminar recordings from six cortical areas in awake mice reveal how layers and rhythms dynamically orchestrate functional streams in vision.     

Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression

The visual cortex in primates is parcellated into cytoarchitectonically, physiologically, and connectionally distinct areas: the striate cortex (V1) and the extrastriate cortex, consisting of V2 and numerous higher association areas [1]. The innervation of distinct visual cortical areas by the thalamus is especially segregated in primates, such that the lateral geniculate (LG) nucleus specifically innervates striate cortex, whereas pulvinar projections are confined to extrastriate cortex [2--8]. The molecular bases for the parcellation of the visual cortex and thalamus, as well as the establishment of reciprocal connections between distinct compartments within these two structures, are largely unknown. Here, we show that prospective visual cortical areas and corresponding thalamic nuclei in the embryonic rhesus monkey (Macaca mulatta) can be defined by combinatorial expression of genes encoding Eph receptor tyrosine kinases and their ligands, the ephrins, prior to obvious cytoarchitectonic differentiation within the cortical plate and before the establishment of reciprocal connections between the cortical plate and thalamus. These results indicate that molecular patterns of presumptive visual compartments in both the cortex and thalamus can form independently of one another and suggest a role for EphA family members in both compartment formation and axon guidance within the visual thalamocortical system.     

Cell type specificity of local cortical connections

The function of the cerebral cortex is dependent on the precise organization of the circuits formed by its component neurons. The connections between neurons are not random, but are specific at multiple levels of organization. For example, each cortical area connects to only a selected subset of other areas and within any given area the axonal and dendritic arbors of individual neurons arborize in precise, layer-specific patterns (for review see Felleman & Van Essen, 1991; Callaway, 1998) . In each layer there are dendrites from multiple cell types including cells with somata both within and outside that layer. Anatomical studies have shown that axons arborizing in a particular cortical layer can connect selectively onto dendrites of some cell types in the layer, while avoiding the dendrites of other cell types (e.g. Freund & Gulyas, 1991; Hornung & Celio, 1992; Staiger et al., 1996). These cell type specific connections are, however, difficult to elucidate with anatomical methods, so the frequency of such specificity has remained elusive. Recent experimental methods combining intracellular recording of single neurons with focal neuronal stimulation by uncaging glutamate with light (“photostimulation”) have made the analysis of cell type specific cortical connections more tractable. These studies show that cell type specificity of connections is prevalent in cortex. Here I review photostimulation-based studies investigating the laminar sources of cortical input to distinct cell types in the visual and somatosensory cortices of rats and the primary visual cortex of monkeys.     

Primary visual cortex and visual awareness

The primary visual cortex (V1) is probably the best characterized area of primate cortex, but whether this region contributes directly to conscious visual experience is controversial. Early neurophysiological and neuroimaging studies found that visual awareness was best correlated with neural activity in extrastriate visual areas, but recent studies have found similarly powerful effects in V1. Lesion and inactivation studies have provided further evidence that V1 might be necessary for conscious perception. Whereas hierarchical models propose that damage to V1 simply disrupts the flow of information to extrastriate areas that are crucial for awareness, interactive models propose that recurrent connections between V1 and higher areas form functional circuits that support awareness. Further investigation into V1 and its interactions with higher areas might uncover fundamental aspects of the neural basis of visual awareness.     

Non-uniformity of extrinsic connections and columnar organization

Afferent columns (>200 μm in diameter) have been intensively investigated in the context of thalamocortical and intrinsic connections. Many extrinsic cortical connections also form columnar terminations, but less is known about their fine organization. Results from intracellular injections of neighboring neurons (in rats: Johnson et al., 2000) suggest that even neurons within a common domain may have non-stereotyped projection patterns, with only partial overlap of terminal arbors. The issue of non-stereotyped projections at the columnar level is further considered by analysis of V1 axons terminating in primate area MT/V5 (an early visual area), and of an axon from temporal cortex terminating in area 7b (a higher cortical area). Both these axons have multiple non-uniform arbors. The implication is that each arbor recruits different numbers and possibly different combinations of postsynaptic elements. While more data are needed concerning convergence of connectional systems, and the actual identity and numbers of postsynaptic targets, the distributed spatial and laminar patterns do not evoke a repetitive uniformity, but rather a columnar substructure and the combinatoric possibilities of the 3-dimensional cortical organization.     

Distinct Parietal and Temporal Pathways to the Homologues of Broca's Area in the Monkey

The homologues of the two distinct architectonic areas 44 and 45 that constitute the anterior language zone (Broca's region) in the human ventrolateral frontal lobe were recently established in the macaque monkey. Although we know that the inferior parietal lobule and the lateral temporal cortical region project to the ventrolateral frontal cortex, we do not know which of the several cortical areas found in those regions project to the homologues of Broca's region in the macaque monkey and by means of which white matter pathways. We have used the autoradiographic method, which permits the establishment of the cortical area from which axons originate (i.e., the site of injection), the precise course of the axons in the white matter, and their termination within particular cortical areas, to examine the parietal and temporal connections to area 44 and the two subdivisions of area 45 (i.e., areas 45A and 45B). The results demonstrated a ventral temporo-frontal stream of fibers that originate from various auditory, multisensory, and visual association cortical areas in the intermediate superolateral temporal region. These axons course via the extreme capsule and target most strongly area 45 with a more modest termination in area 44. By contrast, a dorsal stream of axons that originate from various cortical areas in the inferior parietal lobule and the adjacent caudal superior temporal sulcus was found to target both areas 44 and 45. These axons course in the superior longitudinal fasciculus, with some axons originating from the ventral inferior parietal lobule and the adjacent superior temporal sulcus arching and forming a simple arcuate fasciculus. The cortex of the most rostral part of the inferior parietal lobule is preferentially linked with the ventral premotor cortex (ventral area 6) that controls the orofacial musculature. The cortex of the intermediate part of the inferior parietal lobule is linked with both areas 44 and 45. These findings demonstrate the posterior parietal and temporal connections of the ventrolateral frontal areas, which, in the left hemisphere of the human brain, were adapted for various aspects of language production. These precursor circuits that are found in the nonlinguistic, nonhuman, primate brain also exist in the human brain. The possible reasons why these areas were adapted for language use in the human brain are discussed. The results throw new light on the prelinguistic precursor circuitry of Broca's region and help understand functional interactions between Broca's ventrolateral frontal region and posterior parietal and temporal association areas.     

Patchy organization and asymmetric distribution of the neural correlates of face processing in monkey inferotemporal cortex

BACKGROUND: It is believed that a face-specific system exists within the primate ventral visual pathway that is separate from a domain-general nonface object coding system. In addition, it is believed that hemispheric asymmetry, which was long held to be a distinct feature of the human brain, can be found in the brains of other primates as well. We show here for the first time by way of a functional imaging technique that face- and object-selective neurons form spatially distinct clusters at the cellular level in monkey inferotemporal cortex. We have used a novel functional mapping technique that simultaneously generates two separate activity profiles by exploiting the differential time course of zif268 mRNA and protein expression. RESULTS: We show that neurons activated by face stimulation can be visualized at cellular resolution and distinguished from those activated by nonface complex objects. Our dual-activity maps of face and object selectivity show that face-selective patches of various sizes (mean, 22.30 mm2; std, 32.76 mm2) exist throughout the IT cortex in the context of a large expanse of cortical territory that is responsive to visual objects. CONCLUSIONS: These results add to recent findings that face-selective patches of various sizes exist throughout area IT and provide the first direct anatomical evidence at cellular resolution for a hemispheric asymmetry in favor of the right hemisphere. Together, our results support the notion that human and monkey brains share a similarity in both anatomical organization and distribution of function with respect to high-level visual processing.     

How are specific connections formed between thalamus and cortex?

During development precise thalamocortical connections are established, with reciprocal connections forming correctly in a laminar pattern as well as between the correct thalamic and cortical areas. Recent evidence suggests that both spatial and temporal cues may account for this specificity.     

Combining structural connectivity and response latencies to model the structure of the visual system

Several approaches exist to ascertain the connectivity of the brain, and these approaches lead to markedly different topologies, often incompatible with each other. Specifically, recent single-cell recording results seem incompatible with current structural connectivity models. We present a novel method that combines anatomical and temporal constraints to generate biologically plausible connectivity patterns of the visual system of the macaque monkey. Our method takes structural connectivity data from the CoCoMac database and recent single-cell recording data as input and employs an optimization technique to arrive at a new connectivity pattern of the visual system that is in agreement with both types of experimental data. The new connectivity pattern yields a revised model that has fewer levels than current models. In addition, it introduces subcortical-cortical connections. We show that these connections are essential for explaining latency data, are consistent with our current knowledge of the structural connectivity of the visual system, and might explain recent functional imaging results in humans. Furthermore we show that the revised model is not underconstrained like previous models and can be extended to include newer data and other kinds of data. We conclude that the revised model of the connectivity of the visual system reflects current knowledge on the structure and function of the visual system and addresses some of the limitations of previous models.     

Social Suppressive Behavior Is Organized by the Spatiotemporal Integration of Multiple Cortical Regions in the Japanese Macaque

Under social conflict, monkeys develop hierarchical positions through social interactions. Once the hierarchy is established, the dominant monkey dominates the space around itself and the submissive monkey tries not to violate this space. Previous studies have shown the contributions of the frontal and parietal cortices in social suppression, but the contributions of other cortical areas to suppressive functions remain elusive. We recorded neural activity in large cortical areas using electrocorticographic (ECoG) arrays while monkeys performed a social food-grab task in which a target monkey was paired with either a dominant or a submissive monkey. If the paired monkey was dominant, the target monkey avoided taking food in the shared conflict space, but not in other areas. By contrast, when the paired monkey was submissive, the target monkey took the food freely without hesitation. We applied decoding analysis to the ECoG data to see when and which cortical areas contribute to social behavioral suppression. Neural information discriminating the social condition was more evident when the conflict space was set in the area contralateral to the recording hemisphere. We found that the information increased as the social pressure increased during the task. Before food presentation, when the pressure was relatively low, the parietal and somatosensory–motor cortices showed sustained discrimination of the social condition. After food presentation, when the monkey faced greater pressure to make a decision as to whether it should take the food, the prefrontal and visual cortices started to develop buildup responses. The social representation was found in a sustained form in the parietal and somatosensory–motor regions, followed by additional buildup form in the visual and prefrontal cortices. The representation was less influenced by reward expectation. These findings suggest that social adaptation is achieved by a higher-order self-regulation process (incorporating motor preparation/execution processes) in accordance with the embodied social contexts.     

Brain maps, great and small: lessons from comparative studies of primate visual cortical organization

In this paper, we review evidence from comparative studies of primate cortical organization, highlighting recent findings and hypotheses that may help us to understand the rules governing evolutionary changes of the cortical map and the process of formation of areas during development. We argue that clear unequivocal views of cortical areas and their homologies are more likely to emerge for "core" fields, including the primary sensory areas, which are specified early in development by precise molecular identification steps. In primates, the middle temporal area is probably one of these primordial cortical fields. Areas that form at progressively later stages of development correspond to progressively more recent evolutionary events, their development being less firmly anchored in molecular specification. The certainty with which areal boundaries can be delimited, and likely homologies can be assigned, becomes increasingly blurred in parallel with this evolutionary/developmental sequence. For example, while current concepts for the definition of cortical areas have been vindicated in allowing a clarification of the organization of the New World monkey "third tier" visual cortex (the third and dorsomedial areas, V3 and DM), our analyses suggest that more flexible mapping criteria may be needed to unravel the organization of higher-order visual association and polysensory areas.     

A computational model for the primate neocortex based on its functional architecture

Experimental evidence has shown that the primate neocortex consists in the main of a set of cortical regions which form a perception hierarchy, an action hierarchy and connections between them. By using a computer science analysis, we develop a computational architecture for the brain in which each cortical region is represented by a computational module with processing and storage abilities. Modules are interconnected according to the connectivity of the corresponding cortical regions. We develop computational principles for designing such a hierarchical and parallel computing system. We demonstrate this approach by proposing a causal functioning model of the brain. We report on results obtained with an implementation of this model. We conclude with a brief discussion of some consequences and predictions of our work.     

A computational model of the development of separate representations of facial identity and expression in the primate visual system

Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE) respond primarily to facial identity, while cells within the superior temporal sulcus (STS) respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC) of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs), with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression.     

Computations in the early visual cortex.

This paper reviews some of the recent neurophysiological studies that explore the variety of visual computations in the early visual cortex in relation to geometric inference, i.e. the inference of contours, surfaces and shapes. It attempts to draw connections between ideas from computational vision and findings from awake primate electrophysiology. In the classical feed-forward, modular view of visual processing, the early visual areas (LGN, V1 and V2) are modules that serve to extract local features, while higher extrastriate areas are responsible for shape inference and invariant object recognition. However, recent findings in primate early visual systems reveal that the computations in the early visual cortex are rather complex and dynamic, as well as interactive and plastic, subject to influence from global context, higher order perceptual inference, task requirement and behavioral experience. The evidence argues that the early visual cortex does not merely participate in the first stage of visual processing, but is involved in many levels of visual computation.     

Complementary and dynamic type II cadherin expression associated with development of the primate visual system

The middle temporal visual area (MT, also known as V5) is a visual association area that is particularly evolved in the primate brain. The MT receives input from the primary visual area (V1), constitutes part of the dorsal visual pathway, and plays an essential role in processing motion. Connections between the MT and V1 in the primate brain are formed after birth, and are related to the maturation of visual system. However, it remains to be determined what molecular mechanisms control the formation and maturation of the visual system. Cadherins are transmembrane proteins, originally isolated as cell adhesion molecules, which have multiple roles in synapse formation and function. To investigate potential involvement of cadherins in development of the primate visual system, we examined type II cadherin expression (cadherin‐6, ‐8, ‐12) in cortical and thalamic visual areas of pre‐ and postnatal brains of the common marmoset (Callithrix jacchus). In the prenatal brain, cadherin‐6 was dominantly expressed in the pulvino‐MT pathway whereas cadherin‐8 was dominant in the lateral geniculate nucleus (LGN)‐V1 pathway. During postnatal development, there was a downregulation of cadherin‐6 and upregulation of cadherin‐8 expression in the MT. The timing of this cadherin exchange preceded the development of V1‐MT connections. Our results suggest the possibility that changes in cadherin expression are involved in the development of the primate visual system, and that a switch in cadherin expression may be a general mechanism to control neural plasticity of highly cognitive abilities.     

Laminar specificity of extrinsic cortical connections studied in coculture preparations.

The formation of specific neural connections in the cerebral cortex was studied using organotypic coculture preparations composed of subcortical and cortical regions. Morphological and electrophysiological analysis indicated that several cortical efferent and afferent connections, such as the corticothalamic, thalamocortical, corticocortical, and corticotectal connections, were established in the cocultures with essentially the same laminar specificity as that found in the adult cerebral cortex, but without specificity of sensory modality. This suggests the existence of a cell-cell recognition system between cortical or subcortical neurons and their final targets. This interaction produces lamina-specific connections, but is probably insufficient for the formation of the modality-specific connections.