To test whether visual experience can affect development of visual behavior in the fruitfly, Drosophila, we measured the visually-guided choice behavior of groups of flies reared in complete darkness, compared with controls reared in a normal light/dark cycle. We used a simple visual preference test, i.e. choice among four different visual targets each consisting of vertical black lines of a particular width on a white background, using a blind testing procedure so that the individual rearing histories were not known by the tester. Both groups of flies were strongly attracted to the vertical lines; however, generally the dark-reared flies were more attracted to the wider stimulus lines than were the control flies. Control experiments in which normally reared adults were kept for several days in darkness showed that the effects of dark-rearing were not simply due to being in darkness, but depended upon the timing of the deprivation. The results indicate that the development of visual behavior can be affected by visual experience in Drosophila and thus open the possibility of using Drosophila for genetic dissection of mechanisms of visual plasticity.

Recent electrophysiological and anatomical experiments in rats and cats have shown that treatment with the neurotrophic factor — nerve growth factor (NGF) — prevents the effects of monocular deprivation (MD) at the level of visual cortex and lateral geniculate nucleus. We tested whether NGF treatment was effective in preventing MD effects on visual behavior of monocularly deprived kittens. Behavioral visual acuity was measured in kittens that had been monocularly deprived and treated intraventricularly with NGF for 2 weeks during the critical postnatal period. The detrimental effects of MD on behavioral visual acuity were found to be largely prevented by NGF treatment.

The effects of changing retinal ganglion cell (RGC) density and availability of presynaptic sites on the development of RGC dendritic arbor in the developing chick retina were contrasted. Visual form deprivation was used to induce ocular enlargement and expanded retinal area resulting in a 20–30% decrease in RGC density. In these retinas, RGC dendritic arbors increased in a compensatory manner to maintain the inner nuclear layer to RGC convergence ratio in a way that is consistent with simple stretching; RGC dendritic arbors become larger with increased branch lengths, but without change in the total number of branches. In the second manipulation, partial optic nerve section was used to produce areas of RGC depletion of approximately 60% in the central retina. This reduction in density is comparable to the density of locations in the normal peripheral retina. In RGC-depleted retinas, dendritic arbor areas of RGCs in the central retina grow to match the size of normal peripheral arbors. In contrast to the expanded case, two measures of intrinsic arbor structure are changed in RGC-depleted retinas; the branch density of RGC dendrites is greater, and the relative areas of the two arbors of bistratified cells are altered. We discuss the potential roles of retinal growth, local RGC density, and availability of presynaptic terminals in the developmental control of RGC dendritic arbor.

The normal postnatal development, the influence of age, and the effects of visual deprivation on the dopamine system in the retina of rhesus monkeys were examined. The lowest level of retinal dopamine was found at birth. By 3–4 weeks of age, the dopamine concentration had more than doubled. This level remained relatively constant in the retinas of older infants and of adult monkeys up to 34 yr of age. The level of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and the activity of tyrosine hydroxylase did not significantly change as a function of age during the postnatal life span.

Monocular occlusion of newborn or infant monkeys for 1–15 months with opaque contact lenses resulted in decreases in the retinal concentrations of dopamine and DOPAC relative to the concentrations in the same animals' unoccluded eyes. Occlusion also resulted in a lower level of tyrosine hydroxylase activity in the retina. Monocular eyelid suture from birth to 15 months of age resulted in less consistent alterations of retinal dopamine and DOPAC levels; tyrosine hydroxylase activity, however, was consistently reduced by lid suture. Thus, dopamine synthesis and metabolism, and the ontogenetic increase of the retinal dopamine level of rhesus monkey are reduced by light deprivation.

We analyzed the immunohistochemical distribution of the two calcium-binding proteins, parvalbumin (PV) and calbindin D-28k (CB), in the primary visual cortex and lateral dorsal geniculate nucleus (dLGN) of monocularly enucleated macaque monkeys (Macaca fascicularis and Macaca nemestrind) in order to determine how the expression of PV and CB is affected by functional inactivity. The monkeys survived 1–17 weeks after monocular enucleation. The distribution pattern of each of the proteins was examined immunocytochemically using monoclonal antibodies and compared with that of the metabolic marker cytochrome oxidase (CO). We recorded manually the number of immunostained neurons and estimated the concentration of immunoreactive staining product using a computerized image-acquisition system. Our results indicate a decrease of approximately 30% in the labeling of PV-immunoreactive (ir) neuropil particularly in those layers of denervated ocular-dominance columns receiving the geniculocortical input. There was no change in the number of PV-ir neurons in any compartment irrespective of the enucleation interval. For CB-ir, we found a 20% decrease in the neuropil labeling in layer 2/3 of the denervated ocular-dominance columns. In addition, a subset of pyramidal CB-ir neurons in layers 2 and 4B, which are weakly stained in control animals, showed decreased labeling. In the dLGN of enucleated animals, PV-ir and CB-ir were decreased only in the neuropil of the denervated layers.

From these results, we conclude that cortical interneurons and geniculate projection neurons still express PV and CB in their cell bodies after disruption of the direct functional input from one eye. The only distinct decrease of PV and CB expression is seen in axon terminals from retinal ganglion cells in the dLGN, and in the axons and terminals of both geniculocortical projection cells and cortical interneurons in the cerebral cortex.

The reports of rod-dominated psychophysical spectral sensitivity from the deprived eye of monocularly lid-sutured (MD) monkeys are intriguing but difficult to reconcile with the absence of any reported deprivation effects in retina. As most studies of MD retina have been from cat, we have examined psychophysically the increment threshold spectral sensitivity of MD cats using both reaction time and simultaneous two-choice behavioral procedures. Although the deprived eyes exhibited an absolute increment threshold sensitivity deficit, both rod and cone spectral sensitivity functions were obtained on large white backgrounds. This normal transition from rod to cone vision, as background luminance increased, was also found in threshold vs. intensity functions. Using their deprived eye, some cats exhibited a rod spectral sensitivity function when a smaller, normally photopic, background was used providing some support for a hypothesis that the rod-dominated spectral sensitivity observed in monkey may represent detection of scattered stimulus light. Alternatively monocular deprivation may reveal a rod-dominated mechanism which exists in monkey but not in cat.

To determine whether central communication of retinal signals is necessary for the development of an experimentally induced myopia, tree shrews were exposed to monocular deprivation (MD) while the action potentials of retinal cells in the deprived eye were blocked with intravitreally injected tetrodotoxin (TTX-MD animals). TTX injections (0.6 μ 3 μL) and MD began about 15 days after eye opening, at the start of the susceptible period for the development of lid-suture myopia. Six injections were given, one every second day to produce 12 days of MD and TTX-blockade. Control TTX animals (TTX-open) received TTX in one eye, but not MD, on the same injection schedule and were always found to be behaviorally unresponsive to visual stimuli through the injected eye indicating that TTX blocked central communication of action potentials. Other control animals received intravitreally injected saline in either an open eye (saline-open), or an MD eye (saline-MD). A sham-injected group (sham-inj-MD) received MD and all anesthetic and surgical manipulations except for penetration of the sclera. In all groups, one eye in each animal was an untreated control.

Two effects were found. All MD groups, including the TTX-MD animals, developed a significant vitreous chamber elongation in the deprived eye, indicating that an experimental myopia developed despite ganglion cell blockade. Thus, retinal mechanisms in tree shrew can detect the presence of a degraded visual image and produce an experimental myopia that does not depend on the receipt of visual messages by central neural structures. In addition, eyes in which the sclera was punctured had smaller vitreous chamber depths than comparable uninjected eyes, indicating that puncturing the sclera reduced the normal elongation. These data suggest that forces within the eye normally contribute to its expansion and may be resisted by the choroid and/or the sclera.

The role of sensory experience in the development and plasticity of the visual system has been widely studied. It has generally been reported that once animals reach adulthood, experience-dependent visual plasticity is reduced. We have found that visual experience is not needed for the refinement of receptive fields (RFs) in the superior colliculus (SC) but instead is necessary to maintain them in adulthood (Carrasco et al., 2005). Without light exposure, RFs in SC of hamsters refine by postnatal day 60 as usual but then enlarge, presumably reducing visual acuity. In this study we examine whether a brief period of light exposure during early postnatal development would be sufficient to prevent RF enlargement in adulthood, and whether prolonged light exposure in adulthood could reverse the deprivation-induced increase in RF size. We found that an early postnatal period of at least 30 days of visual experience was sufficient to maintain refined RFs in the adult SC. Prolonged visual experience in adulthood could not reverse the RF enlargement resulting from long-term dark rearing, reflecting a loss of plasticity at this age. Our results suggest that, unlike in visual cortex, dark rearing does not indefinitely extend the critical period of plasticity in SC. Rather, there is a limited time window when early experience can protect RFs from the detrimental effects of visual deprivation in adulthood. These results contribute to understanding adult brain plasticity and argue for the importance of early visual experience in protecting the adult visual system.

Neurons in the superficial layers of the midbrain superior colliculus (SC) exhibit distinct tuning properties for visual stimuli, but, unlike neurons in the geniculocortical visual pathway, most respond best to visual stimuli that are smaller than the classical receptive field (RF). The mechanism underlying this size selectivity may depend on the number and pattern of feedforward retinal inputs and/or the balance between inhibition and excitation within the RF. We have previously shown that chronic blockade of NMDA receptors (NMDA-R), which increases the convergence of retinal afferents onto SC neurons, does not alter size selectivity in the SC. This suggests that the number of retinal inputs does not determine size selectivity. Here we show, using single unit extracellular recordings from the SC of normal hamsters, that size selectivity in neurons selective for small stimulus size is correlated with the strength of inhibition within the RF. We also show that dark rearing causes concomitant reductions in both inhibition and size selectivity. In addition, dark rearing increases the percentage of neurons non-selective for stimulus size. Finally, we show that chronic blockade of NMDA-R, a procedure that does not alter size tuning, also does not change the strength of inhibition within the RF. Taken together, these results argue that inhibition within the RF underlies selectivity for small stimulus size and that inhibition must be intact for size tuning to be preserved after developmental manipulations of activity. In addition, these results suggest that regulation of the balance between excitation and inhibition within the RF does not require NMDA-R activity but does depend on visual experience. These results suggest that developmental experience influences neural response properties through an alteration of inhibitory circuitry.

When normal binocular visual experience is disrupted during postnatal development, it affects the maturation of cortical circuits and often results in the development of poor visual acuity known as amblyopia. Two main factors contribute to the development of amblyopia: visual deprivation and reduced binocular competition. We investigated the affect of these two amblyogenic factors on the expression of the NMDAR1 subunit in the visual cortex because activation of the NMDA receptor is a key mechanism of developmental neural plasticity. We found that disruption of binocular correlations by monocular deprivation promoted a topographic loss of NMDAR1 expression within the cortical representations of the central visual field and the vertical and horizontal meridians. In contrast, binocular deprivation, which primarily affects visual deprivation, promoted an increase in NMDAR1 expression throughout the visual cortex. These different changes in NMDAR1 expression can be described as topographic and homeostatic plasticity of NMDA expression, respectively. In addition, the changes in NMDA expression in the visual cortex provide a greater understanding of the neural mechanisms that underlie the development of amblyopia and the potential for visual recovery.

Monocular deprivation early in postnatal development leads to anatomical and physiological changes in the lateral geniculate nucleus (LGN) and visual cortex. Many of these changes are dependent upon activation of the NMDA receptor. We have examined the role of visual experience in modifying NMDAR1 subunit expression in the LGN of animals reared with various forms of visual deprivation. Following monocular deprivation initiated either at eye opening or at the peak of the critical period, there were approximately 20% fewer NMDAR1-immunopositive neurons in the deprived laminae of the LGN. The loss of NMDAR1-immunopositive neurons was found throughout both the binocular and monocular segments of the LGN and after monocular deprivation until just 3 weeks of age. These results indicate that the loss of NMDAR1 in the LGN following monocular deprivation does not simply reflect changes in the visual cortex. The loss of NMDAR1 expression was not necessarily permanent. Initiation of binocular vision at the peak of the critical period ameliorated the effect of monocular deprivation and the introduction of a period of reverse occlusion led to a complete reversal. Taken together, the results show that the expression of the NMDAR1 subunit in the LGN can be modified by the pattern of visual experience during postnatal development.