Robust Visual Responses and Normal Retinotopy in Primate Lateral Geniculate Nucleus following Long-term Lesions of Striate Cortex

Abstract

Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the LGN. In primates, these lesions also lead to scotomas, within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure. A possible contribution of LGN neurons to blindsight is predicated on two conditions: that the neurons that survive degeneration remain visually responsive, and that their receptive fields continue to represent the region of the visual field inside the scotoma. We tested these conditions in male and female marmoset monkeys (Callithrix jacchus) with partial V1 lesions at three developmental stages (early postnatal life, young adulthood, old age), followed by long recovery periods. In all cases, recordings from the degenerated LGN revealed neurons with well-formed receptive fields throughout the scotoma. The responses were consistent and robust, and followed the expected eye dominance and retinotopy observed in the normal LGN. The responses had short latencies and preceded those of neurons recorded in the extrastriate middle temporal area. These findings suggest that the pathway that links LGN neurons to the extrastriate cortex is physiologically viable and can support residual vision in animals with V1 lesions incurred at various ages.SIGNIFICANCE STATEMENT Patients with a lesion of the primary visual cortex (V1) can retain certain visually mediated behaviors, particularly if the lesion occurs early in life. This phenomenon ("blindsight") not only sheds light on the nature of consciousness, but also has implications for studies of brain circuitry, development, and plasticity. However, the pathways that mediate blindsight have been the subject of debate. Recent studies suggest that projections from the LGN might be critical, but this finding is puzzling given that the lesions causes severe cell death in the LGN. Here we demonstrate in monkeys that the surviving LGN neurons retain a remarkable level of visual function and could therefore be the source of the visual information that supports blindsight.

Keywords: LGN; blindsight; lesion; marmoset; plasticity; primate.

Figure 1.

The spatial extents of the physiological scotomas (the areas shaded in gray) were estimated by manually mapping the receptive fields of V1 neurons (indicated by rectangles) close to the edge of the lesions. In Cases WA5 and WG4, the upper visual field boundaries of the physiological scotoma were estimated from the recording sites in the LGN, using the point where the background activity abruptly increased.

Figure 2.

A–C, Coronal histological sections (processed for cytochrome oxidase) from 3 cases (1 case from each lesion group). Left, The LGN ipsilateral to the V1 lesion. Right, The contralateral LGN. Sections were chosen where the size of the LGN was maximal. D, White arrow indicates an electrode tract through indicates an electrode tract through the LGN. E, White arrow indicates an electrolytic lesion made during the recording. Black arrows indicate the boundaries of the lesion projection zones. D, Dorsal; L, lateral; PE, external parvocellular layer; PI, internal parvocellular layer; MI, internal magnocellular layer; ME, external magnocellular layer.

Figure 3.

Examples of quantitatively mapped receptive fields of LGN neurons. Except for F, the receptive fields were inside the physiological scotomas. Color scale represents above-spontaneous firing rates in response to a flashing square stimulus displayed at the 12 × 12 locations. Red-yellow color scale (A, B, E) represents stimulation through the ipsilateral eye. Blue color scale (C, D, F) represents stimulation through the contralateral eye. The PSTHs are also plotted for each of the 12 × 12 locations. Oval-shaped contours indicate the estimated boundaries of the receptive fields. E, The map was measured with a flashing blue square because a flashing white square was not able to elicit reliable responses. All other receptive fields were mapped with a flashing white square. The visual field coordinates of the centers of each panel are as follows: A, (9.0°,1.5°); B, (17.8°, 3.4°); C, (27.8°, 8.7°); D, (49.4°, 17°); E, (16.0°,12.0°); F, (61.0°, 29.6°).

Figure 4.

Representative progressions of receptive fields of LGN neurons sampled during vertical electrode penetrations, in the infant group. A, Receptive fields encountered in three penetrations in Case W2E. Ovals with solid boundaries represent receptive fields quantitatively mapped. Ovals with dashed boundaries represent receptive fields qualitatively mapped with a manually operated stimulus. Receptive fields driven only by the contralateral (ipsilateral) eye are shaded in blue (orange). Unit α was binocular. Unit 2 and b-e, indicated with labels in cyan-colored boxes, mapped with a flashing blue square. Others were mapped with a flashing white square. Dashed region shaded in light gray represents the estimated physiological scotoma. B, C, Tracings of coronal sections of the LGN. Layers shaded in blue represent contralateral-eye dominated layers (layer PE and ME). Layers shaded in orange represent ipsilateral-eye dominated layers (layer PI and MI). Regions shaded in lighter colors represent the lesion projection zones. The section illustrated in B was 0.6 mm caudal to the one illustrated in C. The penetration site for units a-h was slightly more rostral (∼0.2 mm) to that for units 1–10. Arrows indicate the surface locations of the electrode penetrations. Circles represent the recording sites associated with the receptive fields in A. Circle filled with black represents a site where no stimulus-evoked responses could be observed. Circles shaded in cyan are associated with receptive fields mapped with blue light in A. D, A larger view of the visual space plotted in A, showing the entire extent of the physiological scotoma. E, Receptive fields encountered during two penetrations in Case W6E, plotted in the same format as in Case W2E. Receptive fields (units 11–13 and o-q) far outside the physiological scotoma are omitted for brevity. F, G, The section illustrated in F was 0.4 mm caudal to the one in G. H, The extent of the scotoma in case W6E. VM, Vertical meridian; HM, horizontal meridian; D, dorsal; L, lateral; PE, external parvocellular layer; PI, internal parvocellular layer; MI, internal magnocellular layer; ME, external magnocellular layer.

Figure 5.

A, D, Progression of receptive fields of LGN neurons sampled during vertical electrode penetrations in the adult group. The format is the same as in Figure 4. Locations of the recording sites are indicated in panels B, C (case WA5) and E, F (case WA6). In case WA5, the sections illustrated in B was 0.96 mm caudal to the one in C. In case WA6, the section illustrated in E was 0.48 mm caudal to the one in F. During the penetration illustrated in E, recording stopped at receptive field 13 without through the rest of the LGN. G, The relationship of the scotoma of WA6 to the visual hemifield.

Figure 6.

A, D, Progression of receptive fields of LGN neurons sampled during vertical electrode penetrations in the late-life group. The format is the same as in Figure 4. Locations of the recording sites are indicated in panels C (case WG3) and F, G (case WG4). For WG3, the most lateral penetration (α-θ) was in a section plane 0.16 mm caudal to the one for the other two penetrations. For WG4, the sections illustrated in F and G were 0.48 mm apart (F was more caudal).

Figure 7.

The PSTHs of representative units recorded in lesion projection zones. The color of the histogram represents the eye dominance of the unit. Light blue represents contralateral eye. Orange represents ipsilateral eye. Horizontal rectangle underneath the x axes represents the time interval during which the stimulus was turned on. White rectangle represents a white stimulus. Blue rectangle represents that a blue stimulus was used. The PSTHs in each column are from units sampled in the same penetration, for 1 case in each of the three groups (A–D: case W6E; E–H: case WA5; I–L: case WG4). The receptive field associated with each unit can be identified in Figures 4–6 by the unit label above each PSTH.

Figure 8.

Additional examples of PSTHs of units recorded in the lesion projection zone. The format is the same as in Figure 7. A, B, Examples of OFF responses. C, D, The response patterns of the same units to a flashing stimulus with the blue filter (top subpanel) and without it (bottom subpanel). B–D, The units do not have corresponding receptive fields in Figure 4–6 because they were not sampled in the penetrations illustrated.

Figure 9.

Receptive field diameters as functions of eccentricity. The diameter was calculated as the diameter of a circular receptive field, whose surface area was matched to the surface area of the fitted oval-shaped receptive field (see Materials and Methods). Data pooled from all 6 cases. A, B, Receptive field diameters of units sampled in the putative parvocellular (A) and the magnocellular layers (B) outside the physiological scotomas. Dashed regression lines indicate values that account for 15% and 85% of the data. A, Inset, The 0.5 quantile regression lines. Green represents parvocellular units. Red represents magnocellular units. C, D, Receptive field diameters for units sampled in the parvocellular (C) and the magnocellular layers (D), inside or on the boundaries of the physiological scotomas. A small population of units sampled in the putative K3 layer is also plotted in D (as blue dots, in contrast to the red dots representing magnocellular units). Dashed lines are the same 0.15 quantile and the 0.85 quantile regression lines plotted in A and B. C, Inset, Regression lines for the median values. Green represents parvocellular units. Red represents magnocellular units. Blue represents K3 units.

Figure 10.

All quantitatively mapped receptive fields, plotted separately for the 6 individual cases. For receptive fields inside or on the boundary of the physiological scotomas, those that were larger than the 0.85 quantile thresholds (Fig. 9A,B) are shaded in green for parvocellular units and red for magnocellular units. Insets, The distributions of receptive field diameters (y axis) against eccentricity (x axis). The scale is identical to that in Figure 9A–D. The receptive fields in the main panels that are shaded in colors are also indicated in the insets using the same color scheme.

Figure 11.

Left, The distributions of response strength for the (top to bottom) parvocellular, K3, and magnocellular units. The distributions are subdivided by the locations of the receptive fields. Blue represents those for units with receptive fields outside the scotomas. Green represents those for units with receptive fields inside or on the boundaries of scotomas. Right, For units with receptive fields inside or on the boundaries of the scotomas, the distributions of response strength for the (top to bottom) parvocellular, K3, and magnocellular units. The distributions are subdivided by the age groups. Orange represents the infant group. Green represents the adult group. Blue represents the late-life group. For units of the same category, if the median values for the subdivisions were not significantly different, the median values for all units in that category are indicated by black arrows. Otherwise, the median values for the subdivisions are indicated by color-coded arrows.

Figure 12.

Left, The raster plots illustrate the responses of 4 representative units to 15 repeats of brief flashing stimulus that covered the receptive fields. They were sampled in (from top to bottom) the lesion projection zones of cortical area MT, the parvocellular, K3, and magnocellular layers of the LGN on the hemisphere ipsilateral to V1 lesion. Horizontal bar below each raster plot represents the time interval during which the stimulus was on. Red vertical bars represent the estimated response latencies (55, 37, 35, and 24 ms from top to bottom). Middle, The distributions of response latencies estimated for units pooled in all 6 cases. For each plot, the population was subdivided into units with receptive fields inside or on the boundaries of the physiological scotoma (green), and units with receptive fields outside the physiological scotoma (blue). Arrows indicate median values. If the difference between the subdivisions was not significant, a black arrow indicates the median value of the laminae. If the difference was significant, two color-coded arrows indicate the median values for the subdivisions. Median values for parvocellular units: 32 ms versus 27 ms (H = 13.6102; p = 0.00016507). Median values for magnocellular units: 24 ms versus 26 ms (H = 9.53708; p = 0.00177862). Right, For units with receptive fields inside or on the boundaries of the physiological scotoma, the distributions are divided according to the age groups. Orange represents infant. Green represents adult. Blue represents late-life.