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Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: It was investigated whether alterations in neuronal structure and function occasioned by strabismic amblyopia also may be reflected in alterations in the expression on Y type neurons of a Cat-301 antibody sensitive antigen in the lateral geniculate nucleus (LGN) and cortex of our cat model of strabismic amblyopia., Methods/results: The percentage of positively labelled cells was reduced in LGN laminae that received input from the deviated eye in strabismic amblyopic cats compared with normal cats. In the strabismic cortex, the density of immunopositive neurons was significantly reduced compared with normal the effect being most pronounced in layer IV., Conclusions: Despite previous physiological recordings indicating a decrease in X-cell associated acuity in strabismic amblyopia, the present findings imply that the changes in the early visual experience occasioned by strabismus also produce specific molecular changes in the Y neuronal class.

ACTIVATION of NMDA (N-methyl-D-aspartate) receptors has recently been proposed as a prerequisite for the induction of experience-dependent modification of visual cortical neurones seen during early postnatal development. A new monoclonal antibody to the NMDA receptor subunit 1 (NMDA-R1) has been used to localize and compare the distribution of the receptors in the primary visual cortex of normal cats and those raised with either amblyopia induced by monocular optical blur or monocular esotropic strabismus. Although all three groups showed densest labelling in layers II-III, a comparison of immunopositive cells at any depth below the cortical surface showed a significantly lower frequency in strabismic and anisometropic cats than in normal cats, but a greater frequency in anisometropic cats that in strabismic animals. There appears to be no direct relationship between the expression of NMDA-R1 receptors and the level of excitability, binocularity or neuronal acuity known to exist in either of these two cat models of amblyopia, thus raising further questions as to the precise nature of the role of NMDA receptors in the processes of visual cortical plasticity.

The neural mechanism of strabismic amblyopia was investigated by recording the spatio-temporal properties of striate cortical neurones of cats raised with a surgically induced esotropia. Multiple pseudo-random flashed or phase-alternating stimuli were used, and through cross-correlation, the Wiener kernels were extracted. This analysis has shown that in neurones which retain binocularity to adulthood, two different neural mechanisms of adaptation to ocular misalignment exist. Some of these neurones become amblyopic, such that the non-deviating eye dominates the response for high spatial frequencies while the strabismic eye dominates at low spatial frequencies. Other neurones adapt through active suppression of the monocular response to stimulation of the strabismic eye when the non-deviating eye is simultaneously stimulated.

The acuities of cells in the primary visual cortex of five tenotomized strabismic cats were measured. Previous behavioural studies have shown such animals to possess a severe amblyopia of approximately 1.5 octaves of spatial frequency, yet the acuities of both retinal ganglion and lateral geniculate X-cells are normal. The receptive fields of the cortical cells sampled were within 5 degrees of the area centralis projection. On average, the acuities of cortical cells driven by the amblyopic eye were nearly 1 octave less than those for the non-deviating eye. However, the best cell acuities for each eye were nearly the same. The relationship between ocular dominance and cell acuity was found to be different for the two eyes despite a symmetrical ocular dominance distribution. The acuity deficit for cells driven through the amblyopic eye was present at all depths along the electrode tracks. We conclude that in this model amblyopia, the initial spatial processing deficit lies in the visual cortex, and most probably in the cells of layer IV. Furthermore, the presence of a few cells driven by the amblyopic eye which can perform nearly as well as those from the fellow eye in processing high spatial frequencies gives new insight into the way in which strabismic and deprivation amblyopias differ.

The acuities of X-cells from the dorsal lateral geniculate nucleus (LGN) were measured in five cats raised with a convergent strabismus, surgically induced by tenotomy. The acuities of cells driven by the strabismic eye were not significantly different from the acuities of cells driven by the non-deviating eye over the range of eccentricities in the visual field studied (from the area centralis to over 20 degrees). The data were also similar to X-cell acuities in the LGN of 3 normal cats. Lowered acuities of LGN X-cells driven by the deviating eye of an esotropic cat in which the strabismus was created by myectomy confirm a previous finding of a retinal locus of amblyopia associated with that preparation. In contrast, the results here implicate the visual cortex as the initial site of the deficit in spatial processing in amblyopia arising from tenotomy strabismus.

1. A convergent or divergent strabismus was induced surgically in eight kittens and a cyclotropia of about 90 deg in two additional kittens. 2. Behavioural measurements were made of the visual acuity of each eye for square-wave gratings. All eight animals that were so tested displayed a reduction of acuity in one eye relative to the other of 1.3-2.5 octaves. 3. The activity of retinal ganglion cells was recorded within the amblyopic eye of six cats, three with a convergent strabismus, two with a divergent strabismus and one with a cyclotropia. Measurements were made of the spatial resolution with 215 on-centre cells for horizontal and vertical gratings. 4. In contrast to other reports, we found the spatial resolution of ganglion cells in the amblyopic eye of the strabismic animals to be comparable to those of normal cats at all retinal eccentricities. In particular there was no evidence for a loss of resolution in the vicinity of the area centralis. 5. Measurement of the cross-sectional area of cells in the lateral geniculate nucleus (l.g.n.) revealed no evidence of cell shrinkage in laminae receiving a projection from the amblyopic eye. 6. Together, these findings lead to the conclusion that the neural deficit responsible for the strabismic amblyopia in these animals did not lie in the retina but rather at more central levels of the visual pathway.

The relative effect of short daily periods of reverse occlusion in promoting recovery from the physiological effect of monocular deprivation in kittens were examined with a view to identifying a neurophysiological basis for the visual improvement observed with minimum occlusion therapy in amblyopia. Kittens were monocularly deprived from near birth until 5 weeks of age, at which time they were reverse-sutured and housed in total darkness. Each kitten received a short period of visual exposure through its initially deprived eye each day for either a fixed number of days or for a constant total visual exposure spread over a different number of exposure sessions. Electrophysiological recordings from single cells in the visual cortex were made the day after the last visual exposure. Kittens that received daily periods of reverse occlusion as brief as 30 min for 20 days showed a substantial degree of reversal of cortical ocular dominance. Other experiments indicated that 20 hr of reverse occlusion distributed over a number of brief daily sessions was far more effective in promoting physiological recovery than the same total period of exposure imposed in only two sessions. In general these results suggest that a given period of reverse occlusion may be more effective in promoting recovery with distributed than with massed periods of occlusion.

Experiments were carried out to determine the effects of different types of experimental strabismus on the acuities of retinal ganglion cells. Six kittens were raised from twenty-one days of age with an esotropia surgically induced by myectomy of the lateral rectus muscle and a large portion of the superior oblique muscle. The results are compared with those, previously reported, from five other cats also made esotropic, but by tenotomy of the lateral rectus. All animals tested behaviourally were amblyopic in the strabismic eye. For square wave gratings, the visual acuities were 1.0 to 2.5 cyc/deg through the strabismic eye compared with 6.0 to 7.5 cyc/deg through the non-deviating eye. The cut-off spatial frequencies were determined for 132 brisk sustained cells from five of the myectomized strabismic cats. There was a loss of approximately 20% in cut-off spatial frequency when compared with both normal and tenotomized cats. A correlate of the physiologically observed difference between the tenotomized cats and the myectomized cats was also found in the morphology of cells in the lateral geniculate nucleus. The tenotomized cats showed no evidence of cell shrinkage in laminae receiving a projection from the amblyopic eye whereas in the myectomized cats large differences were observed in cell cross-sectional areas between laminae receiving input from the amblyopic eye and those receiving input from the non-deviating eye. Together, these findings indicate that the presence of a neural deficit in the retina of strabismic cats is associated with the actual removal of extra-ocular muscle and probably has little to do with the optical quality of images arriving at the retina.

Both behavioural and neurophysiological changes can be observed in cats that have experienced interference with their normal visual environment. This visual deprivation may result from alterations to the path of light forming the normal image on the retina, and includes changes that cause the image to fall on an inappropriate part of the retina so that normal binocular interactions are affected. While some neurophysiological changes can be observed at the level of the lateral geniculate nucleus they become more prominent as information reaches the visual cortex, where cells commonly receive neural excitation from both eyes and require the information to come from corresponding parts of the two retinas and that the stimulus should have appropriate orientation and direction of movement. Many of the observations of deprivation in animals have clear parallels in the human environment. [ABSTRACT FROM AUTHOR]