Local sensitivity to stimulus orientation and spatial frequency within the receptive fields of neurons in visual area 2 of macaque monkeys.

We used dynamic dense noise stimuli and local spectral reverse correlation methods to reveal the local sensitivities of neurons in visual area 2 (V2) of macaque monkeys to orientation and spatial frequency within their receptive fields. This minimized the potentially confounding assumptions that are inherent in stimulus selections. The majority of neurons exhibited a relatively high degree of homogeneity for the preferred orientations and spatial frequencies in the spatial matrix of facilitatory subfields. However, about 20% of all neurons showed maximum orientation differences between neighboring subfields that were greater than 25 deg. The neurons preferring horizontal or vertical orientations showed less inhomogeneity in space than the neurons preferring oblique orientations. Over 50% of all units also exhibited suppressive profiles, and those were more heterogeneous than facilitatory profiles. The preferred orientation and spatial frequency of suppressive profiles differed substantially from those of facilitatory profiles, and the neurons with suppressive subfields had greater orientation selectivity than those without suppressive subfields. The peak suppression occurred with longer delays than the peak facilitation. These results suggest that the receptive field profiles of the majority of V2 neurons reflect the orderly convergence of V1 inputs over space, but that a subset of V2 neurons exhibit more complex response profiles having both suppressive and facilitatory subfields. These V2 neurons with heterogeneous subfield profiles could play an important role in the initial processing of complex stimulus features.

Neuronal responses in visual area V2 (V2) of macaque monkeys with strabismic amblyopia.

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

Postnatal development of disparity sensitivity in visual area 2 (v2) of macaque monkeys.

Macaque monkeys do not reliably discriminate binocular depth cues until about 8 wk of age. The neural factors that limit the development of fine depth perception in primates are not known. In adults, binocular depth perception critically depends on detection of relative binocular disparities and the earliest site in the primate visual brain where a substantial proportion of neurons are capable of discriminating relative disparity is visual area 2 (V2). We examined the disparity sensitivity of V2 neurons during the first 8 wk of life in infant monkeys and compared the responses of V2 neurons to those of V1 neurons. We found that the magnitude of response modulation in V2 and V1 neurons as a function of interocular spatial phase disparity was adult-like as early as 2 wk of age. However, the optimal spatial frequency and binocular response rate of these disparity sensitive neurons were more than an octave lower in 2- and 4-wk-old infants than in adults. Consequently, despite the lower variability of neuronal firing in V2 and V1 neurons of infant monkeys, the ability of these neurons to discriminate fine disparity differences was significantly reduced compared with adults. This reduction in disparity sensitivity of V2 and V1 neurons is likely to limit binocular depth perception during the first several weeks of a monkey's life.

Development of temporal response properties and contrast sensitivity of V1 and V2 neurons in macaque monkeys.

The temporal contrast sensitivity of human infants is reduced compared to that of adults. It is not known which neural structures of our visual brain sets limits on the early maturation of temporal vision. In this study we investigated how individual neurons in the primary visual cortex (V1) and visual area 2 (V2) of infant monkeys respond to temporal modulation of spatially optimized grating stimuli and a range of stimulus contrasts. As early as 2 wk of age, V1 and V2 neurons exhibited band-pass temporal frequency tuning. However, the optimal temporal frequency and temporal resolution of V1 neurons were much lower in 2- and 4-wk-old infants than in 8-wk-old infants or adults. V2 neurons of 8-wk-old monkeys had significantly lower optimal temporal frequencies and resolutions than those of adults. Onset latency was longer in V1 at 2 and 4 wk of age and was slower in V2 even at 8 wk of age than in adults. Contrast threshold of V1 and V2 neurons was substantially higher in 2- and 4-wk-old infants but became adultlike by 8 wk of age. For the first 4 wk of life, responses to high-contrast stimuli saturated more readily in V2. The present results suggest that although the early development of temporal vision and contrast sensitivity may largely depend on the functional maturation of precortical structures, it is also likely to be limited by immaturities that are unique to V1 and V2.

Effects of perceptual learning on local stereopsis and neuronal responses of V1 and V2 in prism-reared monkeys.

Visual performance improves with practice (perceptual learning). In this study, we sought to determine whether or not adult monkeys reared with early abnormal visual experience improve their stereoacuity by extensive psychophysical training and testing, and if so, whether alterations of neuronal responses in the primary visual cortex (V1) and/or visual area 2 (V2) are involved in such improvement. Strabismus was optically simulated in five macaque monkeys using a prism-rearing procedure between 4 and 14 wk of age. Around 2 yr of age, three of the prism-reared monkeys ("trained" monkeys) were tested for their spatial contrast sensitivity and stereoacuity. Two other prism-reared monkeys received no training or testing ("untrained" monkeys). Microelectrode experiments were conducted around 4 yr of age. All three prism-reared trained monkeys showed improvement in stereoacuity by a factor of 7 or better. However, final stereothresholds were still approximately 10-20 times worse than those in normal monkeys. In V1, disparity sensitivity was drastically reduced in both the trained and untrained prism-reared monkeys and behavioral training had no obvious effect. In V2, the disparity sensitivity in the trained monkeys was better by a factor of approximately 2.0 compared with that in the untrained monkeys. These data suggest that the observed improvement in stereoacuity of the trained prism-reared monkeys may have resulted from better retention of disparity sensitivity in V2 and/or from "learning" by upstream neurons to more efficiently attend to residual local disparity information in V1 and V2.

Cortical effects of brief daily periods of unrestricted vision during early monocular form deprivation.

Experiencing daily brief periods of unrestricted vision during early monocular form deprivation prevents or reduces the degree of resulting amblyopia. To gain insight into the neural basis for these "protective" effects, we analyzed the monocular and binocular response properties of individual neurons in the primary visual cortex (V1) of macaque monkeys that received intermittent unrestricted vision. Microelectrode-recording experiments revealed significant decreases in the proportion of units that were dominated by the treated eyes, and the magnitude of this ocular dominance imbalance was correlated with the degree of amblyopia. The sensitivity of V1 neurons to interocular spatial phase disparity was significantly reduced in all treated monkeys compared with normal adults. With unrestricted vision, however, there was a small but significant increase in overall disparity sensitivity. Binocular suppression was prevalent in monkeys with constant form deprivation but significantly reduced by the daily periods of unrestricted vision. If neurons exhibited consistent responses to stimulation of the treated eye, monocular response properties obtained by stimulation of the two eyes were similar. These results suggest that the observed protective effects of brief periods of unrestricted vision are closely associated with the ability of V1 neurons to maintain their functional connections from the deprived eye and that interocular suppression in V1 may play an important role in regulating synaptic plasticity of these monkeys.

Effect of onset age of strabismus on the binocular responses of neurons in the monkey visual cortex.

PURPOSE: By 6 weeks of age, neurons in the monkey's primary visual cortex acquire qualitatively adult-like binocular response properties and behaviorally stereopsis emerges. In this study, it was determined whether the onset of strabismus has a more severe impact on cortical binocularity before or after this critical developmental age. METHODS: Infant monkeys were fit with a light-weight helmet which held a total of 27 diopters of base-in prisms in front of their two eyes for a fixed period of two weeks. For one group of infant monkeys, prism-rearing began at 2 weeks of age and for a second group, the onset was at 6 weeks of age. Immediately after the rearing period, i.e., at 4 weeks and 8 weeks of age, respectively, extracellular single-unit recording methods were used to determine the nature and severity of alterations in the binocular response properties of V1 neurons. Dichoptic sinewave gratings were used as visual stimuli. RESULTS: In comparison to normal age-matched infants, V1 neurons in both strabismic groups exhibited reductions in sensitivity to interocular spatial phase disparities (disparity sensitivity) and a higher prevalence of binocular inhibitory interactions (binocular suppression). However, the reduction in disparity sensitivity and the magnitude of binocular suppression were much greater in the late (6-8 weeks) than the early (2- 4 weeks) onset group. CONCLUSIONS: Discordant binocular signals due to brief periods of early strabismus have more serious effects on the development of binocular properties of V1 neurons if they occur shortly after rather than before the emergence of stereopsis (i.e., when the binocular connections are relatively more mature but the visual cortex still shows a high degree of plasticity).

The role of visual experience in the cortical topographic map reorganization following retinal lesions.

The mature visual cortex is capable of reorganizing its functional connections in response to retinal injuries. Although this phenomenon is well established, there are a number of unresolved issues. This paper will review some of the more critical aspects of adult plasticity including those based on our most recent findings. Our preliminary data indicate that a large-scale reorganization of cortical maps following retinal injuries may require an increase in synaptic strengths at key cortical sites promoted by long-term, repeated use.

Nasotemporal directional bias of V1 neurons in young infant monkeys.

PURPOSE: Optokinetic nystagmus (OKN) in young infants typically shows a temporal-to-nasal asymmetry under monocular viewing conditions. The neural basis for this asymmetry has been a matter of debate. One idea is that the OKN asymmetry reflects a similar asymmetry in the directional sensitivity of primary visual cortical (V1) neurons. An alternative hypothesis is that the OKN asymmetry is due to an immaturity in the ability of cortical neurons to influence the activity of subcortical structures that directly control OKN. We addressed this issue by studying the directional sensitivity of V1 neurons in young infant monkeys. METHODS: The neuronal activity of V1 units was recorded from anesthetized and paralyzed rhesus monkeys ranging in age from 6 days to 8 weeks using standard extracellular single-unit recording methods. For comparison, V1 units from normal adult monkeys were also studied. Using drifting sinusoidal gratings of the optimal spatial frequency and a moderate contrast, we measured the responsiveness of individual units to 24 directions of stimulus movement. The preferred stimulus direction and the magnitude of the directional response bias were determined by a vector summation method. RESULTS: No clear signs of nasotemporal asymmetries in direction tuning were found in our cell population from infant monkeys. However, the overall directional sensitivity and the peak monocular response amplitudes of these units were significantly lower, and binocular suppression was greater during the first 4 weeks of life than in adults. CONCLUSIONS: The OKN asymmetry in young infants may be more closely associated with the lower overall directional sensitivity and the subnormal responsiveness of V1 neurons rather than with an obvious asymmetry in the directional properties of V1 neurons.

Residual binocular interactions in the striate cortex of monkeys reared with abnormal binocular vision.

We investigated the nature of residual binocular interactions in the striate cortex (V1) of monkey models for the two most common causes of visual dysfunction in young children, specifically anisometropia and strabismus. Infant rhesus monkeys were raised wearing either anisometropic spectacle lenses that optically defocused one eye or ophthalmic prisms that optically produced diplopia and binocular confusion. Earlier psychophysical investigations had demonstrated that all subjects exhibited permanent binocular vision deficits and, in some cases, amblyopia. When the monkeys were adults, the responses of individual V1 neurons were studied with the use of microelectrode recording techniques while the animals were anesthetized and paralyzed. The manner in which the signals from the two eyes were combined in individual cells was investigated by dichoptically stimulating both eyes simultaneously with drifting sine wave gratings. In both lens- and prism-reared monkeys, fewer neurons had balanced ocular dominances and greater numbers of neurons were excited by only one eye. However, many neurons that appeared to be monocular exhibited clear binocular interactions during dichoptic stimulation. For the surviving binocular neurons, the maximum binocular response amplitudes were lower than normal; fewer neurons, particularly complex cells, were sensitive to relative interocular spatial phase disparities; and the remaining disparity-sensitive neurons exhibited lower degrees of binocular interaction. In prism-reared monkeys, an unusually high proportion of complex cells exhibited binocular suppression during dichoptic stimulation. Binocular contrast summation experiments showed that for both cooperative and antagonistic binocular interactions, contrast signals from the two eyes were combined by individual neurons in a normal linear fashion in both lens- and prism-reared monkeys. The observed binocular deficits appear to reflect a reduction in functional inputs from one eye and/or spatial imprecision in the monocular receptive fields rather than an aberrant form of binocular interaction. In the prism-reared monkeys, the predominance of suppression suggests that inhibitory connections were, however, less susceptible to diplopia and confusion than excitatory connections. Overall, there were many parallels between V1 physiology in our monkey models and the residual vision of humans with anisometropia or strabismus.

Binocular spatial phase tuning characteristics of neurons in the macaque striate cortex.

We employed microelectrode recording techniques to study the sensitivity of individual neurons in the striate cortex of anesthetized and paralyzed monkeys to relative interocular image disparities and to determine the effects of basic stimulus parameters on these cortical binocular interactions. The visual stimuli were drifting sine wave gratings. After the optimal stimulus orientation, spatial frequency, and direction of stimulus movement were found, the cells' disparity tuning characteristics were determined by measuring responses as a function of the relative interocular spatial phase of dichoptic grating pairs. No attempts were made to assess absolute position disparities or horizontal disparities relative to the horopter. The majority (approximately 70%) of simple cells were highly sensitive to interocular spatial phase disparities, particularly neurons with balanced ocular dominances. Simple cells typically demonstrated binocular facilitation at the optimal phase disparity and binocular suppression for disparities 180 degrees away. Fewer complex cells were phase selective (approximately 40%); however, the range of disparity selectivity in phase-sensitive complex cells was comparable with that for simple cells. Binocular interactions in non-phase-sensitive complex cells were evidenced by binocular response amplitudes that differed from responses to monocular stimulation. The degree of disparity tuning was independent of a cell's optimal orientation or the degree of direction tuning. However, disparity-sensitive cells tended to have narrow orientation tuning functions and the degree of disparity tuning was greatest for the optimal stimulus orientations. Rotating the stimulus for one eye 90 degrees from the optimal orientation usually eliminated binocular interactions. The effects of phase disparities on the binocular response amplitude were also greatest at the optimal spatial frequency. Thus a cell's sensitivity to absolute position disparities reflects its spatial tuning characteristics, with cells sensitive to high spatial frequencies being capable of signaling very small changes in image disparity. On the other hand, stimulus contrast had relatively little effect on a cell's disparity tuning, because response saturation occurred at the same contrast level for all relative interocular phase disparities. Thus, as with orientation tuning, a cell's optimal disparity and the degree of disparity selectivity were invariant with contrast. Overall, the results show that sensitivity to interocular spatial phase disparities is a common property of striate neurons. A cell's disparity tuning characteristics appear to largely reflect its monocular receptive field properties and the interocular balance between excitatory and inhibitory inputs. However, distinct functional classes of cortical neurons could not be discriminated on the basis of disparity sensitivity alone.

Postnatal development of binocular disparity sensitivity in neurons of the primate visual cortex.

In macaque monkeys, the age at which neurons in the primary visual cortex (V1) become sensitive to interocular image disparities, a prerequisite for stereopsis, is a matter of conjecture. To resolve this fundamental issue in binocular vision development, we measured the responsiveness of individual V1 neurons in anesthetized and paralyzed infant monkeys as a function of the relative, interocular, spatial phase of dichoptic sine-wave gratings. We found that an adult-like proportion of units were sensitive to interocular image disparity as early as the sixth postnatal day, several weeks before the onset age for stereopsis in monkeys. The ocular dominance distributions of cells in infant monkeys were also indistinguishable from those of adults. Thus, at or only a few days after birth, V1 neurons are capable of combining neural signals from the two eyes as in adults and are sensitive to interocular image disparities. However, the monocular spatial-frequency response properties of these disparity-sensitive units were immature, and their overall responsiveness was far lower than that in adults. During the first 4 postnatal weeks, both the spatial frequency response properties and the peak response amplitude rapidly improved, which resulted in a corresponding increase in the absolute sensitivity of individual units to interocular disparity. The results demonstrate that early binocular vision development in monkeys is not constrained by a paucity of disparity-sensitive V1 neurons but, instead, by the relative immaturity of the spatial response properties and the overall unresponsiveness of existing disparity-sensitive neurons.

Orientation anisotropy and strabismus.

Monocular contrast sensitivity (CS) measurements were obtained in the two principal meridians of eight constant unilateral strabismic subjects and four subjects diagnosed with alternating strabismus. The results indicated that: (1) the CS of both the fellow and deviating eyes of patients with a constant unilateral deviation is significantly less than that of visually normal eyes at high spatial frequencies; (2) both the fellow and deviating eyes reveal a significant reduction in CS to vertically oriented gratings. This effect is frequency-specific, occurring only at the highest spatial frequencies; (3) the magnitude of the orientation anisotropy did not vary systematically with the degree of amblyopia; and (4) a mild orientation anisotropy was observed in only three of the eight alternating strabismic eyes tested. The etiology of the vertical effect is examined with respect to the role of anomalous binocular competition, suppression and abnormal eye movements.

Binocularity in prism-reared monkeys.

Prismatic binocular dissociation in infant monkeys mimicked a concomitant squint. Within 3 weeks, the numbers of binocular neurons in the primary visual cortex were reduced by half and did not recover with up to 5 years of subsequent unrestricted binocular visual experience. The monkeys failed to show binocular summation for spatial contrast sensitivity tasks and were unable to utilise horizontal binocular disparities in random-dot stereograms-two indices of stereoblindness. Electrophysiological analysis of the V1 and V2 cortices showed a dramatic reduction in binocular neurons. Analysis of interocular spatial phase tuning functions showed a conspicuous loss of excitatory binocular drive in V1 neurons which was sufficient to account for many of the defects in binocular function.

Transfer characteristics of lateral geniculate nucleus X neurons in the cat: effects of spatial frequency and contrast.

1. The dependence of signal transfer in the lateral geniculate nucleus (LGN) on stimulus spatial frequency and contrast was investigated by comparing responses of individual X cells with their direct retinal inputs. 2. We used extracellular single-cell recording methods to isolate action potentials (LGN) and S potentials (SPs) from individual neurons in layers A and A1 of anesthetized and paralyzed cats. The stimuli were drifting sinusoidal gratings that were presented at each neuron's preferred orientation. The effects of stimulus spatial frequency and contrast on retinogeniculate signal transfer were determined by comparing the amplitude of the fundamental Fourier responses measured for a cell's action potentials (LGN) and its retinal input (SP) and calculating the transfer ratio (LGN amplitude/SP amplitude) for each stimulus condition. 3. In all units, the LGN response amplitude was lower than that of its retinal input regardless of stimulus spatial frequency. The mean transfer ratio measured at the peak spatial frequency for individual units was 0.56 +/- 0.03 (SE). For the majority of X LGN neurons, however, the efficiency of signal transfer varied considerably with stimulus spatial frequency. The average transfer ratio increased monotonically from 0.08 cycle/deg to near the high cutoff spatial frequency. 4. The effects of stimulus contrast on geniculate signal transfer were far more complex than previously reported and varied substantially between individual neurons. At low stimulus contrasts (< 10%), where all units exhibited linear response characteristics, only one third of our sample showed a monotonic decrease in transfer ratio with increasing stimulus contrast. The remaining two thirds either exhibited proportionately greater signal transfer for higher stimulus contrasts, or signal transfer remained relatively unchanged with increasing stimulus contrasts. When stimulus contrasts exceeded 10%, where response amplitude began to saturate, the transfer ratio was relatively constant in all units and independent of stimulus contrast. 5. Our results demonstrate that signal transfer from retina to visual cortex is regulated by LGN neurons in a stimulus-dependent manner, which appears to reflect the complex interactions between local membrane mechanisms and extraretinal inputs.

Transfer characteristics of X LGN neurons in cats reared with early discordant binocular vision.

1. The effects of early discordant binocular vision on the functional development of the cat lateral geniculate nucleus (LGN) were investigated by quantitatively comparing responses of individual LGN neurons with their direct retinal inputs. 2. Unilateral convergent strabismus (esotropia) was surgically induced in 11 kittens at the age of 3 wk. After the animals had reached 9 mo of age, extracellular microelectrode recordings were made from individual X LGN units in lamina A and A1 of anesthetized and paralyzed cats. Responses were measured for drifting sinusoidal gratings. Within-unit comparisons of LGN action potentials (LGN output) and S potentials (retinal input) were performed to determine the nature of signal transfer in the units driven by the deviating (N = 42) or nondeviating eyes (N = 29) of strabismic cats. The results were compared with similar data (N = 29) obtained from nine normal control cats. 3. The spatial resolution of many individual LGN units in strabismic cats was abnormally reduced relative to their retinal inputs. These differences were more pronounced in units that received inputs from the nasal retina of the contralateral eye. The resolution loss was closely associated with a dramatic decrease in the strength of the receptive field center mechanism of LGN units relative to their retinal inputs. Moreover, the efficiency of signal transfer for high-spatial-frequency stimuli, determined by the transfer ratio (response amplitude of LGN action potentials/amplitude of S potentials), was significantly lower in strabismic cats compared with normal controls. 4. In strabismic cats, contrast thresholds for the action potentials of individual LGN units were significantly higher than those determined for the S potentials. In normal cats, the input-output differences in contrast threshold were negligible. The observed contrast sensitivity loss was more pronounced for high-spatial-frequency stimuli. 5. The speed of signal transfer was significantly decreased in the LGNs of strabismic animals. The visual response latencies of many, but not all, X LGN cells in the strabismic cats were abnormally long when compared with those in normal control units, whereas SP latencies were virtually the same for strabismic and normal cats. Abnormal latencies were prevalent in units that exhibited contrast threshold deficits, and were more severe among the units receiving input from the contralateral nasal retina. 6. The deficits in strabismic cats were found in the LGN units innervated by the deviating and nondeviating eyes. However, for the majority of response measures, the units innervated by the deviating eyes showed notably larger deficits. 7. We conclude that the fidelity of signal transfer from the retina to the LGN is significantly reduced in cats reared with discordant binocular visual experience. Thus the adverse effects of early strabismus are not confined, at least in cats, to the visual cortex.

Adult plasticity in the visual system.

When visual cortical neurons in adult mammals are deprived of their normal afferent input from retinae, they are capable of acquiring new receptive fields by modifying the effectiveness of existing intrinsic connections, a basis for topographic map reorganization. To gain insights into the underlying mechanisms and functional significance of this adult plasticity, we measured the spatial limits and time course of retinotopic map reorganization. We also determined whether reactivated neurons exhibit normal receptive field properties. We found that virtually all units in the denervated zone of cortex acquired new receptive fields (i.e., there were no silent areas in the cortex) and map reorganization can take place within hours of deafferentation provided that retinal lesions are relatively small (< 5 degrees). Furthermore, after long periods of recovery, reactivated units exhibited strikingly normal selectivity to stimulus orientation, direction of movement, and spatial frequency if relatively high contrast stimuli were used. However, responsiveness of these neurons, measured in terms of the maximum response amplitude and the contrast threshold, was clearly reduced. Thus, contrary to traditional belief, the adult visual cortex is capable of exhibiting considerable plasticity, and reactivated neurons are capable of contributing to an analysis of a visual scene.

Receptive-field properties of deafferentated visual cortical neurons after topographic map reorganization in adult cats.

When neurons in primary visual cortex of adult cats and monkeys are deprived of their normal sources of activation by matching lesions in the two retinas, they are capable of acquiring new receptive fields based on inputs from regions of intact retina around the lesions. Although these "reactivated" neurons respond to visual stimuli, quantitative studies of their response characteristics have not been attempted. Thus, it is not known whether these neurons have normal or abnormal features that could contribute to or disrupt an analysis of a visual scene. In this study, we used extracellular single-unit recording methods to investigate their stimulus selectivity and responsiveness. Specifically, we measured the sensitivity of individual neurons to stimulus orientation, direction of drift, spatial frequency, and contrast. Over 98% of all units in the denervated zone of cortex acquired new receptive fields after 3 months of recovery. Newly activated units exhibited strikingly normal orientation tuning, direction selectivity, and spatial frequency tuning when high-contrast (< 40%) stimuli were used. However, contrast thresholds of most neurons were abnormally elevated, and the maximum response amplitude under optimal stimulus conditions was significantly reduced. The results suggest that the striate cortical neurons reactivated during topographic reorganization are capable of sending functionally meaningful signals to more central structures provided that the visual scene contains relatively high contrast images.

Binocular interactions in striate cortical neurons of cats reared with discordant visual inputs.

The postnatal development of cortical binocularity is known to be adversely affected by early abnormal visual experience. However, little information exists on how the signals from the two eyes are combined in individual cortical neurons of animals reared with early discordant binocular visual experience. Since this is a fundamental issue in understanding visual cortical development, we used extracellular single-unit recording methods to study binocular integration in striate cortical neurons of strabismic cats. Specifically, we measured the sensitivity of individual cells to the relative interocular spatial phase of dichoptically presented drifting sinusoidal gratings (i.e., to binocular retinal image disparity). Clear alterations in ocular dominance were observed in all strabismic subjects. Nevertheless, the majority of cortical neurons exhibited some form of binocular interactions when both eyes were stimulated together. The most prominent aspect of cortical physiology in the strabismic animals was the relatively high prevalence of suppressive binocular interactions. Suppression was most frequently found in kittens reared with 2 weeks of early optical dissociation and among adult cats that received 2 weeks of early optical dissociation and a prolonged recovery period. However, substantial excitatory binocular interactions were also maintained in these animals. With an extended period of interocular misalignment (3 or 8 months), all forms of binocular interactions, excitatory and suppressive, were drastically reduced and a greater number of neurons were truly monocular. Although the reduction in the strength of binocular interactions occurred in all units irrespective of their monocular spatial properties, the effect was more pronounced among those units tuned to higher spatial frequencies and this spatial-frequency-dependent effect was larger in the subjects receiving longer periods of binocular dissociation. The results suggest that the "breakdown" of cortical binocular properties in strabismic subjects is not an all-or-none process, and that suppressive binocular interactions may be closely associated with the abnormal binocular interactions exhibited by strabismic humans. Furthermore, our findings are consistent with the notion that cortical disparity-detecting mechanisms are spatial-frequency dependent and, thus, can be selectively altered depending on an animal's early visual experience.

Early discordant binocular vision disrupts signal transfer in the lateral geniculate nucleus.

The mammalian lateral geniculate nucleus (LGN) is known to regulate signal transfer from the retina to the brain neocortex in a highly complex manner. Besides inputs from the brainstem, extraretinal inputs via corticogeniculate projections and local inhibitory neurons modulate signal transfer in the LGN. However, very little is known about whether the postnatal development of LGN signal-transfer mechanisms is influenced by early discordant binocular vision. By intraunit comparisons of responses between individual X-LGN cells and their direct retinal inputs, the efficiency of signal transfer was found permanently reduced due to an early interocular misalignment (strabismus). The contrast sensitivity and spatial resolution of cat LGN cells were significantly lower relative to their retinal inputs, and there was substantial decrease in signal-transfer speed. The observed physiological deficits were associated with immature X-retinogeniculate axon arbors. Thus, contrary to previous ideas, conflicting binocular inputs can produce neural deficits in subcortical visual structures.