Péter Buzás

Model-based analysis of excitatory lateral connections in the visual cortex

Excitatory lateral connections within the primary visual cortex are thought to link neurons with similar receptive field properties. Here we studied whether this rule can predict the distribution of excitatory connections in relation to cortical location and orientation preference in the cat visual cortex. To this end, we obtained orientation maps of areas 17 or 18 using optical imaging and injected anatomical tracers into these regions. The distribution of labeled axonal boutons originating from large populations of excitatory neurons was then analyzed and compared with that of individual pyramidal or spiny stellate cells. We demonstrate that the connection patterns of populations of nearby neurons can be reasonably predicted by Gaussian and von Mises distributions as a function of cortical location and orientation, respectively. The connections were best described by superposition of two components: a spatially extended, orientation‐specific and a local, orientation‐invariant component. We then fitted the same model to the connections of single cells. The composite pattern of nine excitatory neurons (obtained from seven different animals) was consistent with the assumptions of the model. However, model fits to single cell axonal connections were often poorer and their estimated spatial and orientation tuning functions were highly variable. We conclude that the intrinsic excitatory network is biased to similar cortical locations and orientations but it is composed of neurons showing significant deviations from the population connectivity rule. J. Comp. Neurol. 499:861–881, 2006.

Axonal topography of cortical basket cells in relation to orientation, direction, and ocular dominance maps

The axonal (bouton) distributions of a layer 4 clutch cell (CC), two layer 3 medium‐sized basket cells (MBC), and a layer 3 large basket cell (LBC) to orientation, direction, and ocular dominance maps were studied quantitatively. 1) The CC provided exclusively local projections (<380 μm from the soma) and contacted a narrow “niche” of functional representations. 2) The two MBCs emitted local projections (75% and 79% of all boutons), which were engaged with isoorientations (61% and 48%) and isodirections, and long‐range projections (25% and 21%, >313 μm and >418 μm), which encountered cross‐orientation sites (14% and 12%) and isoorientation sites (7% and 5%). Their direction preferences were mainly perpendicular to or opposite those of local projections. 3) The LBC provided the majority (60%) of its boutons to long‐range distances (>437 μm). Locally, LBC boutons showed a rather balanced contribution to isoorientations (19%) and cross‐orientations (12%) and preferred isodirections. Remotely, however, cross‐orientation sites were preferred (31% vs. 23%) and the directional output was balanced. 4) Monte Carlo simulations revealed that the differences between the orientation specificity of local and long‐range projections cannot be explained by a homogeneous lateral distribution of the boutons. 5) There was a similar eye preference in the local and long‐range projection fields of the MBCs. The LBC contacted both contra‐ and ipsilateral eye domains. 6) The basket axons showed little laminar difference in orientation and direction topography. The results suggest that an individual basket cell can mediate a wide range of effects depending on the size and termination pattern of the axonal field. J. Comp. Neurol. 437:259–285, 2001.

Geniculocortical relay of blue-off signals in the primate visual system

A fundamental dichotomy in the subcortical visual system exists between on- and off-type neurons, which respectively signal increases and decreases of light intensity in the visual environment. In primates, signals for red-green color vision are carried by both on- and off-type neurons in the parvocellular division of the subcortical pathway. It is thought that on-type signals for blue-yellow color vision are carried by cells in a distinct, diffusely projecting (koniocellular) pathway, but the pathway taken by blue-off signals is not known. Here, we measured blue-off responses in the subcortical visual pathway of marmoset monkeys. We found that the cells exhibiting blue-off responses are largely segregated to the koniocellular pathway. The blue-off cells show relatively large receptive fields, sluggish responses to maintained contrast, little sign of an inhibitory receptive-field surround mechanism, and negligible functional input from an intrinsic (melanopsin-based) phototransductive mechanism. These properties are consistent with input from koniocellular or “W-like” ganglion cells in the retina and suggest that blue-off cells, as previously shown for blue-on cells, could contribute to cortical mechanisms for visual perception via the koniocellular pathway.

Transmission of blue (S) cone signals through the primate lateral geniculate nucleus

This study concerns the transmission of short‐wavelength‐sensitive (S) cone signals through the primate dorsal lateral geniculate nucleus. The principal cell classes, magnocellular (MC) and parvocellular (PC), are traditionally segregated into on‐ and off‐subtypes on the basis of the sign of their response to luminance variation. Cells dominated by input from S‐cones (‘blue‐on and blue‐off’) are less frequently encountered and their properties are less well understood. Here we characterize the spatial and chromatic properties of a large sample of blue‐on and blue‐off neurons and contrast them with those of PC and MC neurons. The results confirm that blue‐on and blue‐off cells have larger receptive fields than PC and MC neurons at equivalent eccentricities. Relative to blue‐on cells, blue‐off cells are less sensitive to S‐cone contrast, have larger receptive fields, and show more low‐pass spatial frequency tuning. Thus, blue‐on and blue‐off neurons lack the functional symmetry characteristic of on‐ and off‐subtypes in the MC and PC pathways. The majority of MC and PC cells received no detectible input from S‐cones. Where present, input from S‐cones tended to provide weak inhibition to PC cells. All cell types showed evidence of a suppressive extra‐classical receptive field driven largely or exclusively by ML‐cones. These data indicate that S‐cone signals are isolated to supply the classical receptive field mechanisms of blue‐on and blue‐off cells in the LGN, and that the low spatial precision of S‐cone vision has origins in both classical and extraclassical receptive field properties of subcortical pathways.

Specificity of M and L Cone Inputs to Receptive Fields in the Parvocellular Pathway: Random Wiring with Functional Bias

Many of the parvocellular pathway (PC) cells in primates show red–green spectral selectivity (cone opponency), but PC ganglion cells in the retina show no anatomical signs of cone selectivity. Here we asked whether responses of PC cells are compatible with “random wiring” of cone inputs. We measured long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cone inputs to PC receptive fields in the dorsal lateral geniculate of marmosets, using discrete stimuli (apertures and annuli) to achieve functional segregation of center and surround. Receptive fields between the fovea and 30° eccentricity were measured. We show that, in opponent PC cells, the center is dominated by one (L or M) cone type, with normally <20% contribution from the other cone type (high “cone purity”), whereas non-opponent cells have mixed L and M cone inputs to the receptive field center. Furthermore, opponent response strength depends on the overall segregation of L and M cone inputs to center and surround rather than exclusive input from one cone type to either region. These data are consistent with random wiring. The majority of PC cells in both foveal (<8°) and peripheral retina nevertheless show opponent responses. This arises because cone purity in the receptive field surround is at least as high as in the center, and the surround in nearly all opponent PC cells is dominated by the opposite cone type to that which dominates the center. These functional biases increase the proportion of opponent PC cells, but their anatomical basis is unclear.

Functional topography of single cortical cells: an intracellular approach combined with optical imaging

Pyramidal cells mediating long-range corticocortical connections have been assumed to play an important role in visual perceptual mechanisms [C.D. Gilbert, Horizontal integration and cortical dynamics, Neuron 9 (1992) 1-13]. However, no information is available as yet on the specificity of individual pyramidal cells with respect to functional maps, e.g., orientation map. Here, we show a combination of techniques with which the functional topography of single pyramidal neurons can be explored in utmost detail. To this end, we used optical imaging of intrinsic signals followed by intracellular recording and staining with biocytin in vivo. The axonal and dendritic trees of the labelled neurons were reconstructed in three dimensions and aligned with corresponding functional orientation maps. The results indicate that, contrary to the sharp orientation tuning of neurons shown by the recorded spike activity, the efferent connections (axon terminal distribution) of the same pyramidal cells were found to terminate at a much broader range of orientations.

Independence of visuotopic representation and orientation map in the visual cortex of the cat

The representations of visual space and stimulus orientation were mapped in the cat primary visual cortex using electrophysiological recordings supplemented with intrinsic signal optical imaging. The majority of units displaced up to 600 µm laterally had overlapping RFs both in orientation domains and around singularities of the orientation map. Quantitative comparison of these units revealed only a weak, positive correlation between the difference in their preferred orientations and RF separations (area 17: r = 0.09; area 18: r = 0.15). The occurrence of nonoverlapping RFs could be accounted for by random RF position scatter rather than by orientation difference between the units. Monte Carlo analysis showed that our findings are compatible with a locally smooth and linear representation of visual space that is not coupled to the representation of stimulus orientation. An important functional implication of the above map relationships is that positional information captured by the retina is faithfully transmitted into the cortex.

One axon-multiple functions: Specificity of lateral inhibitory connections by large basket cells

The functional specificity of the projections of single large basket cells of the cat primary visual cortex was studied using novel analytical approaches. The distribution of the labelled axons and that of the target cells were three-dimensionally reconstructed and compared quantitatively to orientation, direction and ocular dominance maps obtained with the intrinsic signal optical imaging technique. Quantitative analysis was carried out (i) for the entire basket cell, (ii) separately, for local and distal projections of the axon and (iii) by dissecting the same axon into two projection fields at the first bifurcation. It was found that although the functional distributions (orientation, direction and ocular dominance) for the entire cell were multi-modal and broadly tuned, individual main branches of the same cell displayed highly specific topography. In the further analysis, 2-dimensional probability density estimates of the target cell distributions revealed clear clustering which may be important for local subfield antagonism. These findings provide support to the idea that the same basket cell mediates several specific receptive field operations depending on the location of the target somata in the functional maps.

Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation

The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajals conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations.

Functional Selectivity of Interhemispheric Connections in Cat Visual Cortex

The functional specificity of callosal connections was investigated in visual areas 17 and 18 of adult cats, by combining in vivo optical imaging of intrinsic signals with labeling of callosal axons. Local injections of neuronal tracers were performed in one hemisphere and eight single callosal axons were reconstructed in the opposite hemisphere. The distributions of injection sites and callosal axon terminals were analyzed with respect to functional maps in both hemispheres. Typically, each callosal axon displayed 2 or 3 clusters of synaptic boutons in layer II/III and the upper part of layer IV. These clusters were preferentially distributed in regions representing the same orientation and the same visuotopic location as that at the corresponding injection sites in the opposite hemisphere. The spatial distribution of these clusters was elongated and its main axis correlated well with the preferred orientation at the injection site. These results demonstrate a specific organization of interhemispheric axons that link cortical regions representing the same orientation and the same location of visual stimuli. Visual callosal connections are thus likely involved in the processing of coherent information in terms of shape and position along the midline of the visual field, which may facilitate the fusion of both hemifields into the percept of a single visual scene.