CD Gilbert

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.

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 cell's own receptive field. These connections may be used to generate larger receptive fields or to produce the inhibitory flanks in other cells' receptive fields.

Anatomical studies in the visual cortex have shown the presence of long- range horizontal connections with clustered axonal collaterals, suggesting interactions over distances of several millimeters. We used cross-correlation analysis in cat striate cortex to detect interactions between cells over comparable distances. Using one cell as a reference, we recorded from other cells with a second electrode at varying distances and looked for correlated firing between the two recording sites. This technique allowed us to combine a physiological measure of the strength and type of connection between cells with a characterization of their receptive field properties. The observed interactions were excitatory, and extended over horizontal distances of several millimeters. Furthermore, the interactions were between orientation columns of like specificity, resulting in a waxing and waning in the strength of interaction as the electrodes passed through different orientation columns. We studied relationships between strength of correlation and other receptive field properties and found a tendency for facilitatory interactions between cells sharing the same eye preference. A large proportion of our correlations was due to common input. This feature, and the similarity of interactions between cells in the same column with the reference cell, suggest a high degree of interconnectivity between and within the columns. As the distance between the two electrodes increased, the overlap of the receptive fields of the cells participating in the interactions gradually diminished. At the furthest distances recorded, the cell pairs had nonoverlapping receptive fields separated by several degrees. The distribution and range of these interactions corresponded to the clustering and extent of the horizontal connections observed anatomically.

The cytochrome oxidase-rich patches or blobs of the monkey striate cortex have been shown to contain cells that have unoriented receptive fields, many of which are color selective. We studied the functional organization of color opponency in the blob regions of the parafoveal representation of the visual cortex. We also examined the patterns of connectivity among blob and nonblob cells by multiple electrode penetrations and cross-correlation analysis. Some of the color-selective cells in the blobs exhibited receptive fields that were similar to those found in the parvocellular layers of the lateral geniculate nucleus (LGN): one type exhibited center-surround spatial and chromatic opponency corresponding to the Type I cell found in the LGN; another had center-only chromatic opponency, corresponding to the Type II cell of the LGN. A blob color-selective cell with no LGN counterpart had center color opponency with a nonchromatically opponent surround antagonism. We termed this cell the "modified Type II" cell. Contrary to previous reports, few true double color-opponent cells were found. Some blob cells previously characterized as double opponent probably belong to our modified Type II category and, unlike true double opponent cells, do not respond well to isoluminant color boundaries. Occasional color-selective oriented cells were either intermixed or in close proximity to blob cells. Neighboring electrode penetrations within the same blob yielded cells of the same color opponency, either red versus green or blue versus yellow, suggesting that individual blobs are dedicated to processing one color opponency. Blobs dedicated to red/green color opponency were 3 times more numerous than blue/yellow blobs. Furthermore, the cells in layer 4C lying beneath blobs of a given color opponency had identical color opponency to the overlying cells in blobs. Cross-correlation analysis of pairs of nonblob, oriented cells in the superficial layers showed interactions between cells with matched orientation and eye preference, at varying horizontal separations. Such interactions are consistent with anatomically demonstrated clustered horizontal connections. Positive cross-correlograms were found between blob cells in the same and in adjacent blobs when the cells' receptive field type, color opponency, and ocular dominance matched. Correlograms also indicated monosynaptic connections from Type II to modified Type II cells of the same color opponency, suggesting that Type II cells may contribute to the construction of the modified Type II fields in the cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Horizontal connections are a principal component of intrinsic cortical circuitry. They arise mainly from pyramidal cells and course parallel to the brain's surface for distances as long as 8 mm, linking columns with shared orientation preference and allowing cells to integrate visual information from outside their receptive fields. We examined the synaptic physiology of the horizontal pathway in slices of the cat's striate cortex and found that activating lateral fibers produced both excitation and inhibition. We recorded the postsynaptic responses of identified pyramidal cells in layer 2 + 3 of area 17 to electrical shocks applied at three sites: in the home column of the impaled neuron either in layer 2 + 3 or 4, or at a lateral distance of 0.9-3 mm in layer 2 + 3. Within the home column, suprathreshold stimuli produced compound EPSPs with action potentials, followed by fast, GABAAergic IPSPs and a slower, GABABergic IPSP. For the distant stimulating site, the threshold response was an EPSP. Stronger shocks frequently evoked a disynaptic, GABAAergic IPSP that truncated the EPSP and could dominate the postsynaptic response. At the resting potential, the horizontally evoked EPSP was too small to elicit spikes. With depolarization of the membrane, however, it grew several hundred-fold. This amplification was blocked by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314), but not by 2-amino-5-phosphonovalerate (APV), indicating that it was mediated by Na+ channels, rather than by NMDA receptors. We propose that the horizontal connections provide the means for stimuli outside the receptive field to modulate activity elicited within its confines. The voltage-dependent enhancement of the laterally evoked EPSP may explain why stimulating the surround by itself fails to drive cells but can facilitate their response to stimuli within the receptive field. The ability to initiate disynaptic inhibition from lateral sites shows that recruiting appropriate groups of horizontal fibers can also have a suppressive effect. Thus, the effect of horizontal input is state dependent, with the size and sign of the laterally evoked response changing according to the balance of converging inputs.