A shape can be more difficult to identify when other shapes are near it. For example, when several grating patches are viewed parafoveally, observers are unable to report the orientation of the central patch. This phenomenon, known as 'crowding,' has historically been confused with lateral masking, in which one stimulus attenuates signals generated by another stimulus. Here we show that despite their inability to report the orientation of an individual patch, observers can reliably estimate the average orientation, demonstrating that the local orientation signals are combined rather than lost. Our results imply that crowding is distinct from ordinary masking, and is perhaps related to texture perception. Under crowded conditions, the orientation signals in primary visual cortex are pooled before they reach consciousness.

Contrast-dependent changes in spatial summation and contextual modulation of primary visual cortex (V1) neuron responses to stimulation of their receptive field reveal long-distance integration of visual signals within V1, well beyond the classical receptive field (cRF) of single neurons. To identify the cortical circuits mediating these long-distance computations, we have used a combination of anatomical and physiological recording methods to determine the spatial scale and retinotopic logic of intra-areal V1 horizontal connections and inter-areal feedback connections to V1. We have then compared the spatial scales of these connectional systems to the spatial dimensions of the cRF, spatial summation field (SF), and modulatory surround field of macaque V1 neurons. We find that monosynaptic horizontal connections within area V1 are of an appropriate spatial scale to mediate interactions within the SF of V1 neurons and to underlie contrast-dependent changes in SF size. Contrary to common beliefs, these connections cannot fully account for the dimensions of the surround field. The spatial scale of feedback circuits from extrastriate cortex to V1 is, instead, commensurate with the full spatial range of center-surround interactions. Thus these connections could represent an anatomical substrate for contextual modulation and global-to-local integration of visual signals. Feedback projections connect corresponding and equal-sized regions of the visual field in striate and extrastriate cortices and cover anisotropic parts of visual space, unlike V1 horizontal connections that are isotropic in the macaque. V1 isotropic connectivity demonstrates that anisotropic horizontal connections are not necessary to generate orientation selectivity. Anisotropic feedback connections may play a role in contour completion.

In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in but normal and disease states.

The responses of neurons in the visual cortex to stimuli presented within their receptive fields can be markedly modulated by stimuli presented in surrounding regions that do not themselves evoke responses. This modulation depends on the relative orientation and direction of motion of the centre and surround stimuli, and it has been suggested that local cortical circuits linking cells with similar stimulus selectivities underlie these phenomena. However, the functional relevance and nature of these integrative processes remain unclear. Here we investigate how such integration depends on the relative activity levels of neurons at different points across the cortex by varying the relative contrast of stimuli over the receptive field and surrounding regions. We show that simply altering the balance of the excitation driving centre and surround regions can dramatically change the sign and stimulus selectivity of these contextual effects. Thus, the way that single neurons integrate information across the visual field depends not only on the precise form of stimuli at different locations, but also crucially on their relative contrasts. We suggest that these effects reflect a complex gain-control mechanism that regulates cortical neuron responsiveness, which permits dynamic modification of response properties of cortical neurons.

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.

We have used small injections of biocytin to label and compare patterns of intraareal, laterally spreading projections of pyramidal neurons in a number of areas of macaque monkey cerebral cortex. In visual areas (V1, V2, and V4), somatosensory areas (3b, 1, and 2), and motor area 4, a punctate discontinuous pattern of connections is made from 200-microns-diameter biocytin injections in the superficial layers. In prefrontal cortex (areas 9 and 46), stripe-like connectivity patterns are observed. In all areas of cortex examined, the width of the terminal-free gaps is closely scaled to the average diameter of terminal patches, or width of terminal stripes. In addition, both patch and gap dimensions match the average lateral spread of the dendritic field of single pyramidal neurons in the superficial layers of the same cortical region. These architectural features of the connectional mosaics are constant despite a twofold difference in scale across cortical areas and different species. They therefore appear to be fundamental features of cortical organization. A model is offered in which local circuit inhibitory "basket" interneurons, activated at the same time as excitatory pyramidal neurons, could veto pyramidal neuron connections within either circular or stripe-like domains; this could lead to the formation of the pattern of lateral connections observed in this study, and provides a framework for further theoretical studies of cerebral cortex function.

The retrograde transport of horseradish peroxidase has been used to identify efferent cells in area 17 of the macaque. Cells projecting to the lateral geniculate nucleus are small to medium sized pyramidal neurons with somata in lamina 6 and the adjacent white matter. The projection to the parvocellular division arises preferentially from the upper half of lamina 6, while that to the magnocellular division arises preferentially from the lower part of the lamina. The projection to both superior colliculus and inferior pulvinar arises from all sizes of pyramidal neurons lying in lamina 58 (Lund and Boothe, '75); at least pyramidal neurons of lamina 5B send collateral axon branches to both destinations. Injections with extensive spread of horseradish peroxidase show that many cells of lamina 4B and the large pyramidal neurons of upper lamina 6 also project extrinsically but their terminal sites have not been identified. Other studies have indicated that cells of laminae 2 and 3 project to areas 18 and 19. Therefore every lamina of the visual cortex, with the exception of those receiving a direct thalamic input, contains cells projecting extrinsically. Further, each lamina projects to a different destination and from Golgi studies can be shown to contain cells with specific patterns of dendritic branching which relate to the distribution of thalamic afferents and to the patterns of intracortical connections. These findings emphasise the significance of the horizontal organisation of the cortex with relation to the flow of information through it and contrast with the current concept of columnar organisation shown in physiological studies.

A study of neuron morphology in Golgi Rapid and Kopsch preparations of area 17 of the monkey has shown three basic cell groups -pyramidal neurons, stellate neurons with spinous dendrites and stellate neurons with spine-free or sparsely spined dendrites. These three neuron groups show different distributions in depth from pia to white matter and differ in their relationship to zones of concentrated termination of geniculo-cortical axons. The neuron type most closely related to the laminae receiving a heavy geniculo-cortical projection is the spinous stellate cell. This cell type is restricted to lamina IV. Included in this zone is the broadest band of geniculecortical axon projection (lamina IVC), the horizontal fiber band (lamina IVB ) comprising the major portion of the stria of Gennari (receiving little or no thalamic projection) and the narrow band of thalamo-cortical fiber termination which occurs superficial to the stria of Gennari (lamina IVA). Pyramidal neuron cell bodies are almost totally excluded from lamina IVC and the apical dendrites of lower pyramidal neurons bear many fewer spines in lamina IVC than in laminae V and VI. The basal dendrites of upper pyramidal cells spread superficial and deep to lamina IVA rather than within it. Spine-free stellate neurons occur at all cortical levels and sparselyspined varieties have not been impregnated in lamina IV, but occur in the other laminae.Three groups of presumed thalamocortical axons have been identified, two of which resemble each other in morphology (having long collaterals which appear to terminate by means of spine-like projections of the axonal surface) but not in distribution. One group of these axons bearing spine-like projections distributes in laminae IVC (principally in the deeper half, IVCP) and IVA; the other is restricted in distribution to the upper half of lamina IVC (IVCa). The third group of thalamocortical axons distributes to lamina I and appears to lack the spine-like projections shown by the other two axon groups.Physiological studies of neuronal activity in the visual cortical areas of the monkey have yielded considerable information as to the functional organization of these areas (Hubel and Wiesel, '68, '70). The physiological study of area 17 (Hubel and Wiesel, '68) shows at least two SYStems of neurons occur, arranged in a series of columns extending from pia to white matter, one system having common receptive field properties within each column, the other system aggregated according to eye dominance. A horizontal organization is also evident corresponding to cortical layering separating simple monocular responses in lamina IV from complex or J. COMP. NEUR., 147; 455-496. hypercomplex binocular responses in laminae 11, 111, V and VI. The morphological substrate of this physiological organization is poorly understood even though detailed light microscopic studies have been made of neuronal morphology in these areas of the cortex (Cajal, 1899, '11; Lorente de N6, '49; Poljak, '57). The complexity of the mammalian neo...