Circuits for local and global signal integration in primary visual cortex

Abstract

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.

Fig. 1.

Estimated extent of corticocortical connectional fields in visual field coordinates. a, Visual field measurements. VM, HM, Vertical and horizontal meridian, respectively. E_c, Retinal eccentricity of the center of the injection site or of the labeled field determined experimentally for all cases by electrophysiological recording.E₊, E₋, estimated retinal eccentricity of RF center of cells at the end points of the axis of the labeled field (see Eq. 2). Dashed circles, Mean RF size of neurons at the eccentricity of the end points of the labeled field, measured experimentally in the same or different animals. D°, estimated linear visuotopic extent of the axis of the labeled field (gray circle diameter). ARF, Aggregate receptive field size of the labeled field's axis, calculated as D° + mean RF size of cells at the end points of the labeled field.b, Cortical measurements.X_c, Cortical location of the injection site or of the center of the labeled field.X₊, X₋, Cortical location of cells at the end points of the labeled field's axis. ΔX₊,ΔX₋, Measured cortical distance of the end points of the labeled field from the center.D_(mm), Measured cortical extent of the axis of the labeled field (gray oval diameter).

Fig. 2.

Extent of RF and surround field for a population of macaque V1 cells. a, Response of a representative V1 neuron to an optimal high-contrast grating patch of increasing diameter (top right symbol). Patch diameter at peak response (left arrow) was taken to be the size of the SF of the cell in b and c (middle function). Patch diameter at asymptotic response (right arrow) was taken to be the size of the surround field of the cell ind and e. b, Distribution of SF diameters for a population of V1 neurons (n = 59), measured as in a. Arrowhead, Mean.c, RF size as a function of retinal eccentricity measured under three different test conditions, each one indicated bysymbols to the right of eachline. Straight lines are regression lines. Middle function, SFs measured using expanding high-contrast (75%) gratings; data from this study (n = 59 cells).Bottom function, Hand-mapped mrf; based on data from Dow et al. (1981). Top function, SFs measured using expanding low-contrast gratings; based on data from Sceniak et al. (1999) and obtained by multiplying our high-contrast SF function (middle function) by 2.3. Stars, Means.d–f, Distributions of surround field diameters for a population of V1 cells measured under three different test conditions, each one indicated by top right symbols.d, Expanding high-contrast optimal grating stimulus, including only cells with suppressive surrounds (n= 59, same cells as in b; note different scale onx-axis in b and d).e, Optimal center grating stimulus surrounded by expanding most suppressive grating stimulus (n = 30, subset of cells in b and d).f, Optimal center grating and most suppressive surround grating stimuli plus blank annulus expanding in the surround (n = 30 cells, same cells as in e).Arrowheads in d–f, Means.

Fig. 3.

Patchy lateral (or horizontal) connections in layers 2/3 of macaque area V1. A surface view 2D composite reconstruction of CTB-labeled connections is shown. The labeled field axes measured 9 × 6 mm. Black oval, CTB uptake zone; blank annulus, region of heavy label. Note anisotropic distribution of overall label. The foveal representation is toward the bottom (lateral V1); the V1–V2 border is to the right (anterior V1). Small square, Labeled patch shown at higher power in the inset. Scale bar, 500 μm (corrected for 30% shrinkage). Inset,High-power drawing of patch in the small square, showing labeled fibers and somata (dots), indicating reciprocity of connections. Scale bar, 100 μm.

Fig. 4.

Cells of origin in area V3 of feedback connections to V1. a, Micrograph (left) of a sagittal section through dorsal V3 (shaded box on theright shows location of the photographed region on the annectant gyrus), showing CTB-labeled cell bodies (arrows) in layers 2/3A and 5/6. Cortical layers are indicated at the bottom; WM, White matter; arrowhead, labeled fibers in layers 4 and 3B (terminals of feedforward connections from V1). The composite surface map for this case is shown in b. The injection site involved V1 layers 1–4C and was made at 6.5° eccentricity in the lower visual field (same injection case as in Figs. 6a, 7a). D, Dorsal; P, posterior. Scale bar, 100 μm. b, Surface view plots of cell label density in the upper (left) and lower (right) layers of dorsal V3, generated using custom software written in Matlab. Color scale represents cell density (numbers are cells per 500 μm²). Bins containing <5% of peak cell density were removed from the image. Label anterior to the crown of the annectant gyrus (purple triangles in a,b) is in area V3A. Purple squares (ina, b), Location of the fundus of the lunate sulcus. The long axis of these feedback fields measured 7.8 mm in the upper layers and 9.8 mm in the lower layers. The visual field map of the lower-layer feedback field is shown in Figure 7a. M, Medial (away from the fovea); P, posterior (toward the V1–V2 border). Scale bar, 1 mm (corrected for 30 and 12% shrinkage in the anteroposterior and mediolateral axis, respectively).

Fig. 5.

Patchy terminal label of feedback connections in layer 4B of V1 arising from a tracer injection in area V3.a, Micrograph of a sagittal section through dorsal area V3, showing a CTB injection site involving all cortical layers (layer 1 is involved in the injection but not in this specific section). The injection was made at 6.4° eccentricity in the lower visual field.1, Layer 1; WM, white matter;AG, annectant gyrus. Scale bar, 200 μm (corrected for 30% shrinkage). b, Micrograph showing a surface view of CTB-labeled terminals and cell bodies (arising from the injection site in a) in a single tissue section cut tangentially through V1 layer 4B. c, 2D composite serial tangential section reconstruction of anterograde (i.e., feedback) terminal label through the whole thickness of layer 4B. Arrowheads inb and c point to the same two patches. Note anisotropic distribution of overall label. The axes of the labeled field measured 13.8 × 8.1 mm. The visual field extent of this layer 4B-labeled field is represented as a gray oval in Figure 8b. Scale bar, 1 mm, for b andc (corrected for 30% shrinkage). Medial, Away from the fovea; Anterior: toward the V1–V2 border.

Fig. 6.

Visuotopic extent of V1 lateral connections.a, Visual field map of a representative CTB injection site and resulting labeled lateral connections in V1 layers 2/3. The injection site was in the lower visual field representation of V1 at 6.5° eccentricity, 4° from the vertical meridian (VM). HM, Horizontal meridian.D° of the V1 connectional field (dashed gray oval, 3 × 3.5°) and ARF size of the V1 injection site (black ovals) were estimated as detailed in Materials and Methods. The black ovals represent ARF sizes computed using three different measures of RF size, each indicated bysymbols as in Figure 2c (aggregate mrf, 1.3 × 1.6°; aggregate high-contrast SF, 1.9 × 2.2°; aggregate low-contrast SF, 3.4 × 3.7°). b, Histogram of the population means (n = 21) of the relative visuotopic extent of labeled V1 lateral connections along the isopolar (black bars) and isoeccentricity (hatched bars) axes of the labeled fields. Data from all layers are pooled together. The visuotopic extent is expressed as the ratio of D° of V1 connections to the ARF size of neurons at the V1 injection site and is shown for each of three different methods of measuring RF (and thus ARF) size (symbols on x-axis, as in Fig.2c). The trend for ratios to be smaller along the isoeccentricity axis of the field was not statistically significant. Error bars indicate SEM. The dashed horizontal linemarks a ratio of 1.

Fig. 7.

Visuotopic extent of retrogradely labeled fields of cells of origin of FB connections in extrastriate cortex.a, Visual field map of FB fields of neurons in layers 5/6 of areas V2 (top left), V3 (middle right), and MT (top right) labeled by a CTB injection through V1 layers 1–4C at 6.5° eccentricity (same injection case as in Fig. 6a). Visual field maps of V1 lateral connections in layers 2/3 (bottom left) and 4B (bottom right) labeled by the same V1 injection are also shown. Gray circles, D° of the connectional fields. Black ovals, aggregate mrf size of neurons at the V1 injection site (1.3 × 1.6° in layers 2/3; 1.1 × 1.2° in layer 4B). Dashed black circles, mean mrf size of cells at the edge of labeled fields. The aggregate mrf size of each connectional field is the sum of the diameter of thegray circle plus the diameter of one dashed black circle. This was estimated as described in Materials and Methods and measured 3.5 × 4.1° (V1 layers 2/3 horizontal connections), 4.1 × 4.8° (V1 layer 4B horizontal connections), 6.1° (V2 FB), 8.7° (V3 FB), and 23.6° (MT FB). The aggregate mrf of retrogradely labeled neuronal FB fields in the upper layers of extrastriate cortex (data not shown) measured 5.4° (V2), 7.6° (V3), and 15.3° (MT). Scale bar, 2°. b, Histogram of the population means of the relative visuotopic extent of labeled layer 5/6 FB fields (black bars) in areas V2 (n = 6), V3 (n = 5), and MT (n = 2), arising from the same V1 tracer injections. The visuotopic extent is expressed as the ratio of the aggregate mrf size of the FB field along its long axis to the aggregate mrf size of neurons at the V1 injection site. White bar, Mean aggregate mrf ratio (3.3 ± 0.24) for V1 lateral connections (n = 21). Note cut on they-axis scale.

Fig. 8.

Visuotopic extent of feedback terminal fields anterogradely labeled in V1 by tracer injections in V2 or V3.a, FB field in V1 arising from a V2 injection.Bottom, Surface-view 2D serial tangential section reconstruction of the FB terminal field in layers 2/3 of V1 labeled by a BDA injection through V2 layers 1–6 at ∼2° eccentricity in the lower visual field. The arrow shows the approximate location of the V1–V2 border [vertical meridian (VM)] and points toward the fovea. Dots 1–9, V1 recording sites; numbers correspond to RFs mapped at the top. Star, Center of CTB V1 injection made at the same retinal eccentricity as the V2 injection. The labeled field axes measured 7.6 × 4 mm. Scale bar, 1 mm (corrected for 8% shrinkage). Top, Visual field map of the BDA-labeled FB terminal field shown at thebottom. Black oval, Estimated aggregate mrf of neurons at the V2 injection site (1.6 × 1.15°); gray oval, estimatedD° of resulting labeled FB terminal field in V1 (1.35°x1°). Dashed rectangles, Three RFs (mrf) at V2 injection site recorded in the same vertical penetration at different cortical depths (L3, L5, L6, V2 cortical layers 3, 5, 6, respectively). Gray rectangles, Four RFs (mrf) at V1 injection site (star at the bottom) recorded in the same vertical penetration in different layers (most superficial in layer 2, deepest in layer 6). Note good overlap of RFs at V1 and V2 injected points, and their location at the center of the FB terminal field. Rectangles 1–9, mrf sizes of neurons at V1 recording sites 1–9 shown at the bottom.Filled black rectangle, Foveal RF mapped to monitor eye movements. Note good agreement between estimated and empirically measured visuotopic extents of connections and injection sites.b, Estimated visuotopic extent of labeled FB terminal fields in V1 layers 4B (gray oval, 7.7 × 5.6°) and 5/6 (dashed gray oval, 7.1 × 5.3°) arising from a CTB injection (black oval, 7.2 × 6.6°) through V3 layers 1–6 at 6.4° eccentricity in the lower visual field. c, Histogram of the population means of the relative visuotopic extent of labeled FB terminal fields in V1 (isopolar axis) arising from V2 or V3 injections. The visuotopic extent is expressed as the ratio of D° of the FB fields to the aggregate mrf size of neurons at the extrastriate injection site. Data from all V1 layers are pooled together.

Fig. 9.

Summary diagram showing the spatial scales of V1 lateral and feedback connections relative to the spatial scales of empirically measured summation receptive field and modulatory surround field of V1 neurons. Gray area, Region over which presentation of stimuli at the same orientation as the center stimulus can suppress the center response to an optimally oriented high contrast stimulus. White area, Region over which presentation of optimally oriented high-contrast stimuli evokes or facilitates a response from the neuron (high-contrast SF). Hatched gray annulus, Region over which presentation of stimuli at the same orientation as the center stimulus can suppress or facilitate the center response to an optimally oriented stimulus depending on the center stimulus contrast. Lateral connections within V1 (red) extend beyond the high-contrast summation field (black circle) and are commensurate with the low-contrast SF (dashed black circle) of the V1 neurons from which they arise. Feedback connections (FB; blue) from extrastriate cortex to V1 are commensurate with the full spatial scale of the SF and surround field. FB from “higher” cortical areas is more extensive than FB from “lower” areas. Both connectional systems (lateral and FB) are patchy in V1. Scale bar, 1°. We have previously proposed a model of how FB and lateral connections might mediate modulation of RF responses (Angelucci et al., 2002). In this model, the output of each excitatory pyramidal neuron (e.g., the center recorded neuron) in V1 is controlled by a local inhibitory neuron having higher response gain and contrast threshold than the pyramid (Lund et al., 1995; Somers et al., 2002). FB and lateral inputs contact directly both neuron types, whereas feedforward inputs are only to the pyramid. The divergent–convergent organization of FB and lateral axons is such that these two systems overlap in space and are active for any stimulus diameter, even for stimuli confined to the RF center. At low contrast, RF excitation predominates; lateral and FB input to the pyramid can be summed from more distant cortical (and visual space) locations before inhibition begins to rise. Suppression of the center neuron response would result from increasing the weight of excitation onto the pyramid and its local inhibitory neuron, either via high-contrast feedforward drive or via lateral and FB inputs, such as by increasing stimulus diameter.