[Show abstract][Hide abstract] ABSTRACT: Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2014; 34(41):13840-54. DOI:10.1523/JNEUROSCI.1992-14.2014 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The neural basis of an oblique effect, a reduced visual sensitivity for obliquely oriented stimuli, has been a matter of considerable debate. We have analyzed the orientation tuning of a relatively large number of neurons in the primary visual cortex (V1) and visual area 2 (V2) of anesthetized and paralyzed macaque monkeys. Neurons in V2 but not V1 of macaque monkeys showed clear oblique effects. This orientation anisotropy in V2 was more robust for those neurons that preferred higher spatial frequencies. We also determined whether V1 and V2 neurons exhibit a similar orientation anisotropy soon after birth. The oblique effect was absent in V1 of 4- and 8-week-old infant monkeys, but their V2 neurons showed a significant oblique effect. This orientation anisotropy in infant V2 was milder than that in adults. The results suggest that the oblique effect emerges in V2 based on the pattern of the connections that are established before birth and enhanced by the prolonged experience-dependent modifications of the neural circuitry in V2.
Journal of Vision 02/2014; 14(2). DOI:10.1167/14.2.3 · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infant primates can discriminate texture-defined form despite their relatively low visual acuity. The neuronal mechanisms underlying this remarkable visual capacity of infants have not been studied in nonhuman primates. Since many V2 neurons in adult monkeys can extract the local features in complex stimuli that are required for form vision, we used two-dimensional dynamic noise stimuli and local spectral reverse correlation to measure whether the spatial map of receptive-field subfields in individual V2 neurons is sufficiently mature near birth to capture local features. As in adults, most V2 neurons in 4-week-old monkeys showed a relatively high degree of homogeneity in the spatial matrix of facilitatory subfields. However, ∼25% of V2 neurons had the subfield map where the neighboring facilitatory subfields substantially differed in their preferred orientations and spatial frequencies. Over 80% of V2 neurons in both infants and adults had "tuned" suppressive profiles in their subfield maps that could alter the tuning properties of facilitatory profiles. The differences in the preferred orientations between facilitatory and suppressive profiles were relatively large but extended over a broad range. Response immaturities in infants were mild; the overall strength of facilitatory subfield responses was lower than that in adults, and the optimal correlation delay ("latency") was longer in 4-week-old infants. These results suggest that as early as 4 weeks of age, the spatial receptive-field structure of V2 neurons is as complex as in adults and the ability of V2 neurons to compare local features of neighboring stimulus elements is nearly adult like.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 02/2013; 33(6):2639-49. DOI:10.1523/JNEUROSCI.4377-12.2013 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuronal spatial frequency tuning in primary visual cortex (V1) substantially changes over time. In both primates and cats, a shift of the neuron's preferred spatial frequency has been observed from low frequencies early in the response to higher frequencies later in the response. In most cases, this shift is accompanied by a decreased tuning bandwidth. Recently, the mouse has gained attention as a suitable animal model to study the basic mechanisms of visual information processing, demonstrating similarities in basic neuronal response properties between rodents and highly visual mammals. Here we report the results of extracellular single-unit recordings in the anesthetized mouse where we analyzed the dynamics of spatial frequency tuning in V1 and the lateromedial area LM within the lateral extrastriate area V2L. We used a reverse-correlation technique to demonstrate that, as in monkeys and cats, the preferred spatial frequency of mouse V1 neurons shifted from low to higher frequencies later in the response. However, this was not correlated with a clear selectivity increase or enhanced suppression of responses to low spatial frequencies. These results suggest that the neuronal connections responsible for the temporal shift in spatial frequency tuning may considerably differ between mice and monkeys.
Journal of Neurophysiology 03/2012; 107(11):2937-49. DOI:10.1152/jn.00022.2012 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Connections of primary (V1) and secondary (V2) visual areas were revealed in macaque monkeys ranging in age from 2 to 16 weeks by injecting small amounts of cholera toxin subunit B (CTB). Cortex was flattened and cut parallel to the surface to reveal injection sites, patterns of labeled cells, and patterns of cytochrome oxidase (CO) staining. Projections from the lateral geniculate nucleus and pulvinar to V1 were present at 4 weeks of age, as were pulvinar projections to thin and thick CO stripes in V2. Injections into V1 in 4- and 8-week-old monkeys labeled neurons in V2, V3, middle temporal area (MT), and dorsolateral area (DL)/V4. Within V1 and V2, labeled neurons were densely distributed around the injection sites, but formed patches at distances away from injection sites. Injections into V2 labeled neurons in V1, V3, DL/V4, and MT of monkeys 2-, 4-, and 8-weeks of age. Injections in thin stripes of V2 preferentially labeled neurons in other V2 thin stripes and neurons in the CO blob regions of V1. A likely thick stripe injection in V2 at 4 weeks of age labeled neurons around blobs. Most labeled neurons in V1 were in superficial cortical layers after V2 injections, and in deep layers of other areas. Although these features of adult V1 and V2 connectivity were in place as early as 2 postnatal weeks, labeled cells in V1 and V2 became more restricted to preferred CO compartments after 2 weeks of age.
The Journal of Comparative Neurology 02/2012; 520(3):544-69. DOI:10.1002/cne.22732 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Neurophysiology 11/2011; 107(4):1094-110. DOI:10.1152/jn.00640.2011 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Providing brief daily periods of unrestricted vision during early monocular form deprivation reduces the depth of amblyopia. To gain insights into the neural basis of the beneficial effects of this treatment, the binocular and monocular response properties of neurons were quantitatively analyzed in visual area 2 (V2) of form-deprived macaque monkeys.
Beginning at 3 weeks of age, infant monkeys were deprived of clear vision in one eye for 12 hours every day until 21 weeks of age. They received daily periods of unrestricted vision for 0, 1, 2, or 4 hours during the form-deprivation period. After behavioral testing to measure the depth of the resulting amblyopia, microelectrode-recording experiments were conducted in V2.
The ocular dominance imbalance away from the affected eye was reduced in the experimental monkeys and was generally proportional to the reduction in the depth of amblyopia in individual monkeys. There were no interocular differences in the spatial properties of V2 neurons in any subject group. However, the binocular disparity sensitivity of V2 neurons was significantly higher and binocular suppression was lower in monkeys that had unrestricted vision.
The decrease in ocular dominance imbalance in V2 was the neuronal change most closely associated with the observed reduction in the depth of amblyopia. The results suggest that the degree to which extrastriate neurons can maintain functional connections with the deprived eye (i.e., reducing undersampling for the affected eye) is the most significant factor associated with the beneficial effects of brief periods of unrestricted vision.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: We report the results of extracellular single-unit recording experiments where we quantitatively analyzed the receptive-field (RF) properties of neurons in V1 and an adjacent extrastriate visual area (V2L) of anesthetized mice with emphasis on the RF center-surround organization. We compared the results with the RF center-surround organization of V1 and V2 neurons in macaque monkeys. If species differences in spatial scale are taken into consideration, mouse V1 and V2L neurons had remarkably fine stimulus selectivity, and the majority of response properties in V2L were not different from those in V1. The RF center-surround organization of mouse V1 neurons was qualitatively similar to that for macaque monkeys (i.e., the RF center is surrounded by extended suppressive regions). However, unlike in monkey V2, a significant proportion of cortical neurons, largely complex cells in V2L, did not exhibit quantifiable RF surround suppression. Simple cells had smaller RF centers than complex cells, and the prevalence and strength of surround suppression were greater in simple cells than in complex cells. These findings, particularly on the RF center-surround organization of visual cortical neurons, give new insights into the principles governing cortical circuits in the mouse visual cortex and should provide further impetus for the use of mice in studies on the genetic and molecular basis of RF development and synaptic plasticity.
The Journal of Comparative Neurology 06/2010; 518(11):2051-70. DOI:10.1002/cne.22321 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mammalian visual system is characterized by a hierarchy of processing stations that tend to preserve and reflect the spatial order of outputs from the retina of each eye. The optic nerve fibers maintain much of the spatial organization as they leave the eye, and refine that order as they terminate in their major brainstem targets: the dorsal lateral geniculate nucleus (LGN) and the superior colliculus. A retinotopic pattern is preserved in the LGN projections to primary visual cortex and in at least several other areas devoted to the early stages of cortical processing of visual information. This chapter considers what happens to these orderly representations of the retinal outputs when some part of the retina is missing.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Neurophysiology 09/2008; 100(5):2486-95. DOI:10.1152/jn.90397.2008 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vision of newborn infants is limited by immaturities in their visual brain. In adult primates, the transient onset discharges of visual cortical neurons are thought to be intimately involved with capturing the rapid succession of brief images in visual scenes. Here we sought to determine the responsiveness and quality of transient responses in individual neurons of the primary visual cortex (V1) and visual area 2 (V2) of infant monkeys. We show that the transient component of neuronal firing to 640-ms stationary gratings was as robust and as reliable as in adults only 2 wk after birth, whereas the sustained component was more sluggish in infants than in adults. Thus the cortical circuitry supporting onset transient responses is functionally mature near birth, and our findings predict that neonates, known for their "impoverished vision," are capable of initiating relatively mature fixating eye movements and of performing in detection of simple objects far better than traditionally thought.
Journal of Neurophysiology 07/2008; 100(3):1476-87. DOI:10.1152/jn.90446.2008 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cortical activity of subjects with compromised central vision (e.g., amblyopes) is thought to be much weaker for stimulation of the affected eye than in the fellow eye. Because these subjects are known to exhibit considerable difficulties in keeping steady fixation, we investigated the effects of anomalous fixation on their multifocal visual-evoked potential (mfVEP) responses using a dual Purkinje image (dPi) eye tracker. Our results show that mfVEP responses to stimulation of the central 5 degrees were depressed in the affected eye compared to those in the normal eye and the magnitude of response reductions was proportional to the degree of visual acuity loss in amblyopic subjects. Fixation was far less stable while viewing with the affected eye than with the fellow eye, some exhibiting jerk nystagmus and/or saccadic oscillations. Normal subjects with artificially imposed nystagmus showed similar reductions of VEP responses. The relative magnitudes of the deficits in mfVEP responses were tightly correlated with the degree of fixation instability. These results suggest that the interpretation of anomalous neural or perceptual processing in amblyopic subjects must take the effects of unsteady fixation during measurements into consideration in order to reveal the true nature and extent of sensory neural deficits.
Journal of Vision 02/2008; 8(3):16.1-14. DOI:10.1167/8.3.16 · 2.39 Impact Factor