George D. Mower

The effect of dark rearing on the time course of the critical period in cat visual cortex

The effects of dark rearing on the time course of the postnatal critical period for monocular deprivation (MD) in visual cortex were determined in cats who experienced 2 days of MD at various postnatal ages. In normal development, plasticity (susceptibility to MD) was very low at 3 weeks, rose sharply at 6 weeks, and gradually declined over the next 10 weeks. This developmental profile was dramatically altered by dark rearing which slowed the entire time course of the critical period. In dark reared cats, plasticity rose steadily over the first 12 weeks, and was maintained at 16 weeks. There was a crossover of the two profiles of the critical period such that at young ages (6 weeks) normal cats were more plastic than dark reared cats while at later ages (after 9 weeks) dark reared cats were more plastic. A second experiment indicated that dark rearing slowed down the progression of the critical period even after it had been initiated by a period of normal vision. MD produced substantial effects after the normal critical period in cats who were reared normally for the first 6-8 weeks of life and then placed in darkness until 5 months of age. The results are discussed in terms of a simple model of the accelerating effect of visual input and the decelerating effect of total darkness on the time course of the critical period.

Comparison of the effects of dark rearing and binocular suture on development and plasticity of cat visual cortex

Comparisons were made between the effects of binocular suture and dark rearing in terms of: (1) the state of visual cortical physiology after prolonged deprivation; and (2) the nature of physiological recovery seen when monocular vision was experienced after prolonged deprivation. These comparisons were based on the ocular dominance distribution and receptive field tuning characteristics of visual cortical cells. After prolonged dark rearing, most visual cortical cells were binocularly activated and had non-specific receptive field properties. Monocular vision after dark rearing produced dramatic changes: the majority of cells were responsive only to the open eye and these cells typically displayed orientation and direction selectivity. Prolonged binocular suture, on the other hand, resulted in a high incidence of unresponsive cells and cells with unmappable receptive fields, and a low proportion of binocularly responsive cells. Monocular vision experienced after binocular suture resulted in only slight physiological changes, and there was no evidence for selective development of connections from the open eye. These results indicate that dark rearing and binocular suture have different effects on the development of cat visual cortical cells. Diffuse visual stimulation through the sutured lids (binocular suture) appears to produce permanent developmental effects on cortical physiology, whereas complete deprivation (dark rearing) leaves cortex in a state which can be modified by subsequent visual experience.

Changes in immediate early gene expression during postnatal development of cat cortex and cerebellum

Postnatal brain development involves interactions between extracellular signals and preprogrammed genetic events. Immediate early genes (IEGs) are a group of genes that are induced by extracellular signals and their protein products alter transcription by binding regulatory elements in other genes. Using Northern and slot blot analysis of total RNA isolated from visual cortex, frontal cortex, and cerebellum of cats, we have determined the postnatal development patterns of mRNA expression for 5 of these genes, c-fos, erg-1, c-jun, jun-B, and c-myc. Each gene had a distinct developmental pattern of mRNA expression, and for a given gene, these patterns were often different in different brain structures. These results suggest that temporal changes in the combinatorial interaction of different IEGs during early postnatal life are important for normal brain development.

Animal models of strabismic amblyopia: Physiological studies of visual cortex and the lateral geniculate nucleus

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.

Microiontophoretic bicuculline restores binocular responses to visual cortical neurons in strabismic cats.

Rearing cats with surgically induced strabismus resulted in an abnormally high percentage (80%) of monocularly driven neurons in visual cortex. Microiontophoretic application of the GABA antagonist bicuculline restored binocular responses to over 50% of these monocular cells. Elevation of spontaneous rate by glutamate failed to produce binocularity. These results indicate that intracortical inhibition plays a role in the abnormal ocular dominance distribution of strabismic cats.

The effects of dark-rearing on the development and plasticity of the lateral geniculate nucleus.

During a prolonged period of dark-rearing, lateral geniculate X-cells developed normal spatial resolving capacities and otherwise normal receptive field properties. Y-cells were reduced in frequency. Neither of these developmental processes were altered by subsequent monocular vision. In visual cortex, on the other hand, both the development of normal receptive field properties and the susceptibility to monocular deprivation were delayed by dark-rearing.

Cat visual corticopontine cells project to the superior colliculus

Abstract Antidromic stimulation was used to study corticopontine visual axons and their tectal collaterals in cats. Sixty-seven cortical cells were activated antidromically by electrical stimulation of the rostral pontine visual area, 38 in area 18, and 29 in lateral suprasylvian cortex. Two thirds of these corticopontine cells (46 cells) could also be antidromically activated by stimulation of the superior colliculus, demonstrating that they gave rise to a tectal collateral.

[3H]muscimol binding of GABA receptors in the visual cortex of normal and monocularly deprived cats

In vitro receptor binding techniques were used to compare the total number, affinity and regional distribution of GABA receptors in visual cortex, as revealed by [3H]muscimol binding, in 5 normal and 5 monocularly deprived (MD) cats. Analysis of saturation kinetics and pharmacological specificity indicated that binding was to a single site having the characteristics of the GABAA receptor. No differences were found between normal and MD cats in either number or affinity of receptors. Within visual cortex, there were laminar differences in the density of binding, but no evidence for a lateral (columnar) organization. Label was densest in the superficial layers (I-IV), lowest in layer V and intermediate in layer VI. This pattern of label varied with incubation parameters with layer IV showing the densest label when high concentrations of [3H]muscimol and short rinse times were used. There were no differences between normal and MD cats in regional distribution of receptors under any incubation condition.

Evidence for an enhanced role of GABA inhibition in visual cortical ocular dominance of cats reared with abnormal monocular experience

The effects of microiontophoretic bicuculline, a gamma-aminobutyric acid (GABA) antagonist, on the ocular dominance of visual cortical neurons were compared in normal cats and cats reared with abnormal monocular visual experience (monocular deprivation, surgical strabismus, and monocular deprivation after dark rearing). Cells that were monocular prior to drug application showed disinhibitory effects on ocular dominance far more frequently than originally binocular cells in all rearing conditions. When the total population of neurons was considered there were marked differences among rearing conditions: only 17% of cells showed change in ocular dominance in normal cats whereas over 50% showed changes in cats reared with abnormal monocular visual experience. These results indicate that GABA inhibition plays an enhanced role in cats with abnormal cortical ocular dominance. The results are interpreted in the context that the GABA system is passively biased by alterations in the pattern of excitatory input to contribute to abnormal patterns of ocular dominance.

Behavioral recovery from binocular deprivation in the cat

Visuo-motor behavior and visual acuity were assessed in animals who experienced monocular vision after a prolonged period of binocular deprivation. In animals who experienced initial binocular suture, there was limited recovery and no difference between the initially opened and late opened eye. In animals who experienced initial dark-rearing, the initially opened eye recovered to normal levels and the late opened eye showed severe amblyopia. These differences in behavioral recovery between dark-rearing and binocular suture are compared with physiological differences between the two rearing conditions.