Evidence that binocular competition affects the postnatal development of Y-cells in the cat's lateral geniculate nucleus

We investigate the effective connectivity in the lateral geniculate nucleus and visual cortex of humans with amblyopia. Six amblyopes participated in this study. Standard retinotopic mapping stimuli were used to define the boundaries of early visual cortical areas. We obtained fMRI time series from thalamic, striate and extrastriate cortical regions for the connectivity study. Thalamo-striate and striate-extrastriate networks were constructed based on known anatomical connections and the effective connectivities of these networks were assessed by means of a nonlinear system identification method. The effective connectivity of all networks studied was reduced when driven by the amblyopic eye, suggesting contrary to the current single-cell model of localized signal reduction, that a significant part of the amblyopic deficit is due to anomalous interactions between cells in disparate brain regions. The effective connectivity loss was unrelated to the fMRI loss but correlated with the degree of amblyopia (ipsilateral LGN to V1 connection), suggesting that it may be a more relevant measure. Feedforward and feedback connectivities were similarly affected. A hemispheric dependence was found for the thalamo-striate feedforward input that was not present for the feedback connection, suggesting that the reduced function of the LGN recently found in amblyopic humans may not be solely determined by the feedback influence from the cortex. Both ventral and dorsal connectivities were reduced.

In the companion study (Dev. Brain Res., 34 (1987) 223–233), we showed that a monocular injection of antibodies against ox large retinal ganglion cells produces a 53% (low concentration) to 82% (high concentration) loss of Y-cells in lateral geniculate nucleus (LGN) layers A and A₁ that receive inputs from the antibody-injected eye. At the same time, the percentage of LGN X-cells is unaffected. In the present study, we investigated the effect of this monocular antibody-induced reduction of LGN Y-cells on the development of ocular dominance in striate cortex. Four-week-old kittens were given an intraocular injection of either a low (110 μg/33 μl volume) or a high (333 μg/33 μl volume) concentration of antibodies and single-cell recordings were carried out in striate cortex 33–65 weeks later. Following an injection of either antibody concentration, we found only slight abnormalities in striate cortex ocular dominance compared to normal adult cats. There was a small, but significant, decrease in the percentage of binocularly driven cells and a concomitant increase in the percentage of cells driven exclusively by the normal or control-injected eye. No ocular dominance abnormalities were found in kittens injected monocularly with control γ-globulins, indicating that the changes are due to effects of the antibodies. The changes in cortical ocular dominance produced by early antibody treatment are very different from those produced by rearing with monocular deprivation (MD) despite a similar loss of LGN Y-cells in the two conditions. This suggests that an initial (primary) monocular loss of LGN Y-cells in young kittens is not sufficient to alter cortical ocular dominance in a manner similar to that found after MD. The results thus argue against the hypothesis that the MD-induced loss of response to the deprived eye in striate cortex is secondary to a Y-cell loss in the LGN.

Five cats monocularly deprived by lid suture between 2 and 3 weeks of age were used experimentally between the ages of 16 and 52 weeks. An intraocular injection of horseradish peroxidase was used to reveal the individual C laminae (C, C1, C2) in the dorsal lateral geniculate nucleus. Soma size measurements of cells in the C laminae showed significant differences between cells in the deprived layers C and C1 and the corresponding nondeprived layers, but not between cells in deprived and nondeprived layer C2.

Visual acuity and visuo-motor behavior were assessed in various models of experimental amblyopia in cats (n = 15). Three models of strabismic amblyopia were studied: surgical esotropia by sectioning one lateral rectus muscle; comitant optical strabismus by rearing cats with goggles which placed a stationary wedge prism before one eye; and incomitant optical strabismus by rearing cats with goggles which placed a rotatable wedge prism before one eye. These cats were compared with normal and monocularly deprived cats.

Clear amblyopic deficits were found in monocularly deprived, esotropic and rotating prism cats. The amblyopic deficits were graded among these preparations, being most severe in monocularly deprived cats and least severe in esotropic cats. The degree of behavioral amblyopia in these preparations was correlated with the extent of physiological abnormalities in visual cortex and the lateral geniculate nucleus. Fixed optical strabismus did not result in behavioral deficits and does not appear to be a good model of strabismic amblyopia. Variable optical strabismus, on the other hand, produced clear deficits in one eye, both behaviorally and physiologically, without impaired ocular motility.

Receptive field properties of visual cortical and lateral geniculate cells were studied in 4 models of amblyopia in the cat: monocular deprivation (MD cats), surgical esotropia (esotropic cats), optically induced concomitant strabismus (stationary prism cats) and optically induced incomitant strabismus (rotating prism cats). Comparison observations were made in normal cats. Recordings in visual cortex indicated a reduction in responsiveness to the treated eye in MD and rotating prism cats. Esotropic and stationary prism cats showed mainly a loss of binocular cells. Recordings in the lateral geniculate nucleus indicated a reduction in the spatial resolving capacity of X-cells driven by the treated eye in MD, esotropic and rotating prism cats. The magnitude of this effect was comparable in all of these preparations. Stationary prism cats showed comparable spatial resolving capacities in X-cells driven by either eye. Y-cells were unaffected in any preparation except MD where there were reduced frequencies of Y-cells driven by the treated eye. These results indicate that: (1) interocular differences in spatial patterns without form deprivation are sufficient to produce a loss of responsiveness to one eye in visual cortex; (2) incomitant disparities are necessary to produce the physiological correlates of amblyopia in cats; and (3) deficits in spatial resolution in geniculate neurons are comparable in magnitude in various amblyopic preparations.