We explore the extent to which neocortical circuits generalize, i.e., to what extent can neocortical neurons and the circuits they form be considered as canonical? We find that, as has long been suspected by cortical neuroanatomists, the same basic laminar and tangential organization of the excitatory neurons of the neocortex is evident wherever it has been sought. Similarly, the inhibitory neurons show characteristic morphology and patterns of connections throughout the neocortex. We offer a simple model of cortical processing that is consistent with the major features of cortical circuits: The superficial layer neurons within local patches of cortex, and within areas, cooperate to explore all possible interpretations of different cortical input and cooperatively select an interpretation consistent with their various cortical and subcortical inputs.

Neuronal circuits of the neocortex

A prominent and stereotypical feature of cortical circuitry in the striate cortex is a plexus of long-range horizontal connections, running for 6-8 mm parallel to the cortical surface, which has a clustered distribution. This is seen for both intrinsic cortical connections within a particular cortical area and the convergent and divergent connections running between area 17 and other cortical areas. To determine if these connections are related to the columnar functional architecture of cortex, we combined labeling of the horizontal connections by retrograde transport of rhodamine-filled latex microspheres (beads) and labeling of the orientation columns by 2-deoxyglucose autoradiography. We first mapped the distribution of orientation columns in a small region of area 17 or 18, then made a small injection of beads into the center of an orientation column of defined specificity, and after allowing for retrograde transport, labeled vertical orientation columns with the 2-deoxyglucose technique. The retrogradely labeled cells were confined to regions of orientation specificity similar to that of the injection site, indicating that the horizontal connections run between columns of similar orientation specificity. This relationship was demonstrated for both the intrinsic horizontal and corticocortical connections. The extent of the horizontal connections, which allows single cells to integrate information over larger parts of the visual field than that covered by their receptive fields, and the functional specificity of the connections, suggests possible roles for these connections in visual processing.

https://www.jneurosci.org/content/jneuro/9/7/2432.full.pdf

Columnar specificity of intrinsic horizontal and corticocortical connections in cat visual cortex

We perceive the visual world as a unitary whole, yet one of the guiding principles of nearly a half century of neurophysiological research since the early recordings by Hartline (1938) has been that the visual system consists of neurons that are driven by stimulation within small discrete portions of the total visual field. These classical receptive fields (CRFs) have been mapped with the excitatory responses evoked by a flashed or moving stimulus, usually a spot or bar of light. Most of the visual neurons, in turn, are organized in a series of maps of the visual field, at least 10 of which exist in the visual cortex in primates as well as additional topographic representations in the lateral geniculate body, pulvinar and optic tectum (Allman 1977, Newsome & Allman 1980, Allman & Kaas 1984). It has been widely assumed that perceptual functions that require the integration of inputs over large portions of the visual field must be either collective properties of arrays of neurons representing the visual field, or features of those neurons at the highest processing levels in the visual system, such as the cells in inferotemporal or posterior parietal cortex that typically possess very large receptive fields and do not appear to be organized in visuotopic maps. These assumptions have been based on the results of the many studies in which receptive fields were mapped with conventional stimuli, presented one at a time, against a featureless background. However, unlike the neurophysiologist's tangent screen, the natural visual scene is rich in features, and there is a growing body of evidence that in many visual neurons stimuli presented outside the CRF strongly and selectively influence neural responses to stimuli presented within the CRF. These results suggest obvious mechanisms for local-global comparisons within visuotopically organized structures. Such broad and specific surround mechanisms could participate in many functions that require the integration of inputs over wide regions of the visual space such as the perceptual constancies, the segregation of figure from ground, and depth perception through motion parallax. In the first section of this paper, we trace the historical development of the evidence of response selectivity for visual stimuli presented beyond the CRF; in the second, examine the anatomical pathways that sub serve these far-reaching surround mechanisms; and in the third, explore the possible relationships between these mechanisms and perception.

Stimulus Specific Responses from Beyond the Classical Receptive Field: Neurophysiological Mechanisms for Local-Global Comparisons in Visual Neurons

The main purpose of this study was to examine the normal postnatal development of ocular dominance columns in the striate cortex of the macaque monkey and to determine how this developmental process is influenced by monocular lid-suture. The physiological pattern of ocular dominance was studied in long, tangential electrode penetrations. For anatomical demonstration of the distribution of afferents we relied principally on the transneuronal transport of [3H]proline injected into one eye, and to a lesser extent on the Liesegang silver method. The effects of deprivation on cell size in the lateral geniculate nucleus (LGN) were also studied. Twenty-six monkeys, divided into 5 groups (A–E), were used.



A
The process of normal columnar development was examined in four monkeys aged from 1 to 6 weeks. At one week, there was both an anatomical and a physiological mixing of left- and right-eye inputs to layer IVC, but the basic columnar pattern was evident, and some small regions were already monccular. At three weeks the columnar pattern resembled that seen in the adult, except for a suggestion that the borders between columns were not so sharply demarcated. By six weeks an adult degree of columnar segregation was established.

B
A series of ten monkeys had monocular suture performed at successively later ages, ranging from 2 days to adult, and they were allowed to survive for a long period. It was found that deprivation begun at any age from birth to about 6 weeks had approximately the same effect: the afferents for the open eye formed greatly expanded columns in layer IVC, and the columns for the closed eye were shrunken and fragmented. In the layers above and below IVC the open eye dominated almost completely. At 10 weeks, closure had only a mild effect on columnar size in layer IVC. With closures at 7–14 months there was no change in the size of columns in layer IVC, but when stained with the Liesegang silver method the deprived-eye columns were paler than those for the open eye, suggesting a lower density of fibers. These late deprivations still caused a shift of ocular dominance in the upper cortical layers but not such an extreme change as with earlier closures. Lid suture in an adult had no detectable anatomical or physiological effects. Even monocular enucleation, in an adult, failed to induce sprouting of the geniculocortical afferents for the remaining eye.

C
In order to investigate the rate at which monocular deprivation produces its effects, six monkeys were examined after short periods of deprivation in infancy. Eye-closure from birth to 3 weeks was sufficient to produce the full anatomical and physiological effects. A nine-day closure at 3 weeks, followed by reopening of the eye, also produced the full effects. A two-week period of deprivation begun at five weeks of age, however, caused relatively mild columnar expansion in layer IVC, suggesting that late closures may require more time to produce anatomical changes than early closures.

D
The effects of reopening the deprived eye and closing the experienced eye (reverse suture) were studied in three monkeys. The initial lid sutures were performed in the first few days of life. With reverse suture a t 3 weeks the relative sizes of the two sets of columns were reversed. This anatomical reversal was, however, limited to the afferents from the parvocellular laminae of the LGN; the magnocellular afferents remained in the pattern induced by the early deprivation. The layers outside of IVC were strongly dominated by the initially deprived eye. Reverse suture at 6 weeks allowed an anatomical recovery of the parvocellular afferents to a normal columnar size, but not a complete reversal. Again, the magnocellular afferents for the initially deprived eye were not induced t o enlarge their territory. Reverse suture at 1 year of age did not lead to any recovery.

E
One monkey was reared in complete darkness from 3 days of age until 7 weeks of age. This animal, studied autoradiographically, showed a normal columnar pattern in layer IVC.





We draw four conclusions from these experiments. (i) Ocular dominance columns are only partially formed a t birth but develop rapidly in the first few weeks of postnatal life. The process of segregation of the left- and right-eye afferents-in layer IV occurs in the presence or absence of visual experience. (ii) This developmental process may be redirected by early monocular deprivation, causing the segregation of the two sets of afferents into columns of unequal width, (iii) A rearrangement of the afferents can be induced for a short period after their segregation is complete. This is true of both normal and deprived animals. (iv) The eye preference of neurons in the upper and lower layers may be changed even after plasticity in layer-IVC is no longer detectable.

The development of ocular dominance columns in normal and visually deprived monkeys.

The intrinsic connections of the cortex have long been known to run vertically, across the cortical layers. In the present study we have found that individual neurons in the cat primary visual cortex can communicate over suprisingly long distances horizontally (up to 4 mm), in directions parallel to the cortical surface. For all of the cells having widespread projections, the collaterals within their axonal fields were distributed in repeating clusters, with an average periodicity of 1 mm. This pattern of extensive clustered projections has been revealed by combining the techniques of intracellular recording and injection of horseradish peroxidase with three- dimensional computer graphic reconstructions. The clustering pattern was most apparent when the cells were rotated to present a view parallel to the cortical surface. The pattern was observed in more than half of the pyramidal and spiny stellate cells in the cortex and was seen in all cortical layers. In our sample, cells made distant connections within their own layer and/or within another layer. The axon of one cell had clusters covering the same area in two layers, and the clusters in the deeper layer were located under those in the upper layer, suggesting a relationship between the clustering phenomenon and columnar cortical architecture. Some pyramidal cells did not project into the white matter, forming intrinsic connections exclusively. Finally, the axonal fields of all our injected cells were asymmetric, extending for greater distances along one cortical axis than along the orthogonal axis. The axons appeared to cover areas of cortex representing a larger part of the visual field than that covered by the excitatory portion of the cell9s own receptive field. These connections may be used to generate larger receptive fields or to produce the inhibitory flanks in other cells9 receptive fields.

https://www.jneurosci.org/content/jneuro/3/5/1116.full.pdf

Clustered intrinsic connections in cat visual cortex

The thalamic projection to the visual cortex has been studied in the cat and monkey by experimental light and electron microscopic techniques. After large lesions of the lateral geniculate nucleus degeneration is confined to the ipsilateral hemisphere. In the cat it is found in areas 17, 18 and 19 and in the lateral suprasylvian area, terminal degeneration occurring predominantly in layer IV, with less in layers I, III and V; fibre degeneration crossing layers VI and V towards layer IV is coarser in area 18 than elsewhere. Some fine horizontal degenerating fibres are seen in layer I. In the monkey terminal degeneration is restricted to area 17; again degenerating fibres ascend to layer IV where there is dense fragmentation, but in contrast to the cat there is also a second, less dense, but distinct, band in layer IIIb. A little fine, horizontal fibre degeneration is present in layer I and there is slight terminal degeneration in this site and in layer V. Electron microscopy shows that degenerating terminals are recognizable in the visual cortex at several stages according to survival period, but that most stages can exist simultaneously in any one site, and that all are associated with asymmetrical membrane thickenings. Mapping of electron microscopic sections confirms the laminar pattern seen with the light microscope. In area 17 of the cat and monkey and in area 19 of the cat over 80% of degenerating terminals end on dendritic spines, the rest making synaptic contact mainly with dendritic shafts, and very few with the soma of stellate cells, but in area 18 some 10% are related to stellate cell bodies. In layer IV of all areas degenerating terminals tend to occur in clusters which are separated by approximately 100 $\mu $m. Where degenerating thalamic afferents end on cell somata or varicose dendrites almost all are identifiable as derived from stellate cells. Although it is difficult to identify positively the parent dendrites bearing the spines which receive the majority of the thalamo-cortical afferents, it is suggested that some, at least, of them may also originate from stellate cells.

An experimental study of the termination of the lateral geniculo-cortical pathway in the cat and monkey.

An experimental neurohistological study has been made of the intrinsic connections of the cortex of area 17 of the monkey, of the commissural connections of the visual cortex of the cat and monkey and of the association fibres passing into area 17 of the cat. In light microscopic studies the axonal degeneration method of Nauta has been used, and the site and mode of termination of the degenerating fibres has also been determined with the electron microscope. After narrow slit lesions through the depth of the cortex of area 17 degeneration of the intrinsic fibre connections does not extend beyond 5-6 mm: this extent is asymmetrical, being 1-2 mm further on one side of the lesion than on the other. In all layers there is intense fine degeneration in a width of 200 $\mu$ m on each side of the lesion and in layer IV no degeneration extends beyond this distance. In all the other layers there is moderate fibre and terminal degeneration for up to 2 mm on one side and 1 mm on the other; in the stria of Gennari fibre degeneration continues for a further 1-2 mm from the lesion, and these fibres probably terminate within the stria and in the immediately adjoining parts of layer IIIb superficially and in layer IV deeply. After a small focal lesion in layers I and II fine degeneration is found in these layers over a total extent of 2-3 mm, and a few fibres pass down into layer III. When the damage extends into layer III, in addition to the horizontal degeneration in this layer there is a moderate degree of fibre degeneration in the stria, in layers V and VI and a few fibres pass into the underlying white matter. If the lesion extends deep enough to involve the stria dense horizontal fibre degeneration appears in it and this extends to a maximum width of 5-6 mm. Similar degeneration in the stria has been found after small lesions restricted to it or within layer IV, indicating that most of the horizontal fibres in the stria arise within the cortex and probably in layer IV (or V and VI). When the lesion reached down to layer V there was an increase in the density of degeneration in layer V itself, in layers II and III, and more degenerating fibres entered the white matter; these observations suggest that many of the fibres in layer V arise in that layer, that there is a recurrent projection from layer V to layers II and III and that most of the efferent fibres from area 17 arise in the deep layers of the cortex. Degenerating fibres which pass vertically up or down from a small lesion in the cortex were confined to a narrow band lying above or below the lesion. Electron microscopic observations are in good agreement with the light microscopy both with respect to the extent of the degeneration and with the variation in the different laminae. The degenerating axon terminals formed only a small proportion of the total number of terminals present, and there was a marked decrease in their number beyond 1 mm from the lesion. The majority (90%) of the terminals had asymmetrical membrane thickenings and most made contact with dendritic spines; others formed synapses upon dendrites and cell somata of stellate cells. Degenerating terminals with symmetrical membrane thickenings formed 10% of the total and the post-synaptic profiles related to these were complementary to those of the asymmetrical terminals, 78% ending on dendrites of both pyramidal and non-pyramidal cells. A small number ended on cell bodies and on initial segments. The degeneration of commissural fibres was studied only at the boundary of areas 17 and 18. With the light microscope it was found that all layers were affected by degeneration in area 18 but that layer IV was clear in area 17. This was confirmed with the electron microscope and it was found that all of the terminals had asymmetrical membrane thickenings and the majority made synaptic contact with dendritic spines. The association fibre connections passing from area 18 into area 17 of the cat were found to terminate only in the lateral part of area 17 and that layer IV was left clear of fragmentation. These fibres have asymmetrical terminals and the majority end on dendritic spines.

The Intrinsic, Association and Commissural Connections of Area 17 of the Visual Cortex

The retrograde cell degeneration in the lateral geniculate nucleus of the cat has been studied after lesions of the visual and adjoining areas of the cortex. Following lesions which are limited to area 17, the medium and small cells of the main laminae of the nucleus degenerate; damage restricted to area 18 does not result in any localized, severe degeneration, but combined destruction of areas 17 and 18 causes all the cells-large, medium and small-of the main laminae and the central interlaminar nucleus to degenerate. Cellular change in the medial interlaminar nucleus is only found after involvement of area 19. When the cortex of the middle suprasylvian gyrus is removed in addition to these areas the degeneration in the lateral geniculate nucleus is much more severe, and there is loss of the laminar pattern due to severe gliosis in the central interlaminar nucleus. There is a well-defined topical organization in the geniculo-cortical projection, and in the antero-posterior dimension it is the same to all areas of the visual cortex, anterior parts of the nucleus projecting anteriorly and posterior parts posteriorly. Medial parts of the main laminae are related to the lateral part of area 17 and to the medial part of area 18, and lateral parts of the laminae project to the medial part of area 17 and to the lateral part of area 18. After partial lesions which involve both areas 17 and 18 the cellular degeneration affects the laminae differentially along their antero-posterior extent, that in lamina A being the most anterior and that in lamina B the most posterior; in sagittal sections such a band, or column, of degeneration passes from antero-superior to postero-inferior at right angles to the plane of the laminae.

The Projection of the Lateral Geniculate Nucleus Upon the Cortex in the Cat

A light and electron microscopic study has been made of areas 17, 18 and 19 of the cat and area 17 of the monkey (Macaca mulatta) . An attempt has been made to clarify the somewhat confusing terminology applied to the laminar cytoarchitectonic pattern of the visual cortex. The cytoarchitectonic features of the subdivisions of the visual cortex of the cat and of area 17 of the monkey have been described. In both animals layer IV is characterized by the predominantly stellate nature of its cells. In the cat the stria of Gennari is situated in the upper part of layer IV and the extreme lower part of layer III, while in the monkey most of it is found outside layer IV, mainly in layer IIIc . There are other horizontally orientated axonal plexuses in layers I, III, V and VI. In Golgi material stellate cells can be classified as large and small 9smooth’, large and small 9spiny’ and small 9intermediate’. Stellate cells with large spines on long pedicles are particularly common in layer IV. A correlation has been made between the features of stellate and pyramidal cells in light and electron microscopic material, and the features of spine-bearing varicose dendrites derived from stellate cells described.

L. J. Garey

Papers

An experimental study of the termination of the lateral geniculo-cortical pathway in the cat and monkey.

The Intrinsic, Association and Commissural Connections of Area 17 of the Visual Cortex

The Projection of the Lateral Geniculate Nucleus Upon the Cortex in the Cat

A light and electron microscopic study of the visual cortex of the cat and monkey.