Monocular deprivation reduces reliability of visual cortical responses to binocular disparity stimuli

While continuous monocular deprivation (MD) of patterned vision causes severe loss of visual cortical responses and visual acuity in the affected eye, these effects can be avoided by providing brief daily periods of binocular exposure [BE; D.E. Mitchell et al. (2003) Curr. Biol ., 8, 1179–1182; D.E. Mitchell et al. (2006) Eur. J. Neurosci ., 23, 2458–2466; D.S. Schwarzkopf et al. (2007) Eur. J. Neurosci ., 25, 270–280]. In order to analyse binocular mechanisms involved in this phenomenon, we studied neuronal responses in primary visual cortex to binocular disparity stimuli in cats that had experienced mixed daily visual exposure (i.e. different amounts of daily binocular and monocular exposure). To examine whether binocular responses are as reliable in MD as in normal animals, we analysed single-trial responses to spatial phase disparity stimuli. In cats with various amounts of daily binocular experience (3.5 h, 7 h or 12 h) alone, about half of neurons (47.9%) showed reliable phase-specific binocular responses in two consecutive trials. The percentage of phase-selective cells was reduced in cats with mixed visual exposure with a decrease in the duration of daily BE. Within these neurons, a 'stable' cell population, i.e. with identical relative phases eliciting the strongest and weakest responses in two trials, was also reduced. In other words, the responses of neurons recorded from deprived animals were more likely to show different preferred phases on successive trials, although their amplitude ratios in both trials were about equal. We suggest that the detrimental effect of MD on binocular vision may begin, at least in part, with a subtle disruption of the mechanism involved in discrimination of binocular disparity signals.     

Brief daily binocular vision prevents monocular deprivation effects in visual cortex

Even short periods of early monocular deprivation result in reduced cortical representation and visual acuity of the deprived eye. However, we have shown recently that the dramatic deprivation effects on vision can be prevented entirely if the animal receives a brief period of concordant binocular vision each day. We examine here the extent to which the cortical deprivation effects can be counteracted by daily periods of normal experience. Cats received variable daily regimens of monocular deprivation (by wearing a mask) and binocular vision. We subsequently assessed visual cortex function with optical imaging of intrinsic signals and visually evoked potential recordings. Regardless of the overall length of visual experience, daily binocular vision for as little as 30 min, but no less, allowed normal ocular dominance and visual responses to be maintained despite several times longer periods of deprivation. Thus, the absolute amount of daily binocular vision rather than its relative share of the daily exposure determined the outcome. When 30 min of binocular exposure was broken up into two 15-min blocks flanking the deprivation period, ocular dominance resembled that of animals with only 15 min of binocular vision, suggesting that binocular experience must be continuous to be most effective. Our results demonstrate that normal experience is clearly more efficacious in maintaining normal functional architecture of the visual cortex than abnormal experience is in altering it. The beneficial effects of very short periods of binocular vision may prevent any long-term effects (amblyopia) from brief periods of compromised vision through injury or infection during development.     

Long- and short-term monocular deprivation in the rhesus monkey: effects on visual fields and optokinetic nystagmus

Monkeys with 1 eyelid sutured within 2 weeks of birth for 7 or 14 d (short-term monocular deprivation, n = 5) or for 18-26 months (long-term monocular deprivation, n = 5) were tested for visual and oculomotor function at approximately 2 years of age. Long-term monocularly deprived animals were behaviorally blind when visual inputs were restricted to the deprived eye. There was no sparing of the monocular segment of the visual field, and optokinetic nystagmus could not be elicited even with vertical stripes up to 15 degrees in width. These behavioral deficits could not be accounted for by optical or retinal abnormalities. In contrast, short-term monocularly deprived animals displayed normal visual fields and optokinetic nystagmus was driven by both eyes. Slow-phase gain was reduced and directional asymmetries were observed when optokinetic stimulation was restricted to the deprived eye.     

Stereoscopic mechanisms in monkey visual cortex: binocular correlation and disparity selectivity

The neural signals in visual cortex associated with positional disparity and contrast texture correlation of binocular images are the subject of this study. We have analyzed the effects of stereoscopically presented luminous bars and of dynamic random-dot patterns on the activity of single neurons in cortical visual areas V1, V2, and V3-V3A of the alert, visually trained rhesus macaque. The interpretation of the results and considerations of possible neural mechanisms led us to recognize 2 functional sets of stereoscopic neurons. (1) A set of neurons, tuned excitatory (T0) or tuned inhibitory (TI), which respond sharply to images of zero or near-zero disparity. Objects at or about the horopter drive the T0 neurons and suppress the TI, while objects nearer and farther have the opposite effects on each type, inhibition of the T0 and excitation of the TI. The activity of these neurons may provide, in a reciprocal way, the definition of the plane of fixation, and the basic reference for binocular single vision and depth discrimination. (2) A second set of neurons includes tuned excitatory at larger crossed or uncrossed disparities (TN/TF) and neurons with reciprocal excitatory and inhibitory disparity sensitivity with cross-over at the horopter (NE/FA). Binocularly uncorrelated image contrast drives these neurons to a maintained level of activity, which shifts, in response to correlated images, toward facilitation or suppression as a function of positional disparity. These neurons may operate in the neural processing leading to stereopsis, both coarse and fine, and also provide signals for the system controlling binocular vergence. These results indicate that cortical visual neurons are binocularly linked to respond to the relative position and contrast of the images over their receptive fields, and also that both these aspects of binocular stimulation may be utilized by the brain as a source of stereoscopic information.     

Monocular deprivation with concurrent sagittal transection of the optic chiasm

We have used monocular deprivation combined with sagittal transection of the optic chiasm (MD-OX) in an attempt to separate the contributions of competitive binocular interactions from those of deprivation per se. Cell body measurements were made in the intact A1 laminae of cats reared with MD-OX. These measurements were compared to matched measurements in normally-reared cats. Cells in the deprived A1 lamina of the MD-OX cats were smaller than normal to a degree consistent with other reports involving BD and MD-E. Also consistent with the absence of competitive imbalances, cells in the non-deprived A1 lamina of these cats were normal in size, exhibiting no sign of hypertrophy.     

Behavioral effects of protein deprivation and rehabilitation in adult rats: relevance to morphological alterations in the hippocampal formation

In the present study we have analyzed the behavioral and neuroanatomical effects of protein deprivation in adult rats. Starting at 2 months of age, animals were maintained on 8%-casein diet either for 8 months (malnourished group), or for 6 months followed by a 2-month period of nutritional rehabilitation (17%-protein diet, rehabilitated group). Malnourished rats exhibited reduced emotional reactivity and impaired habituation in the open field. In a water maze, these animals did not differ from controls during training, but showed retention deficits on the probe trial. However, working memory, sensorimotor abilities and passive avoidance behavior were not significantly impaired in malnourished rats. The performance of rehabilitated group was similar to that of the control group throughout behavioral testing. Postmortem morphological analysis revealed that the total number of neurons in the granular layer of the dentate gyrus, and in CA3 and CA1 hippocampal fields was reduced in protein-deprived and rehabilitated rats relative to controls. In addition, it was found that protein deprivation caused a 30% loss of synapses established between mossy fibers and dendrites of CA3 pyramidal cells, whereas nutritional rehabilitation resulted in a reversal of this effect. These results show that prolonged malnutrition in adult rats produces marked loss of hippocampal neurons and synapses accompanied by substantial impairments of hippocampal-dependent behaviors. The fact that nutritional rehabilitation results in restoration of the total number of hippocampal synapses and parallel amelioration of the behavioral impairments suggests that the mature CNS possesses a remarkable potential for structural and functional recovery from the damage induced by this type of dietary insult.     

Visual split brain and monocular deprivation in kittens: differentiation between the effects of disuse and of binocular competition in visual cortex cells

To differentiate between the resulting effect of disuse, developmentally induced by deprivation, and the binocular competition effect on cortical cells, visual split brain was performed concurrently with monocular deprivation in kittens. In the experienced hemisphere of the split brain deprived cats (ipsilaterally to the non-deprived eye), there were twice as many visually responsive cortical cells than found in their inexperienced hemisphere (ipsilaterally to the deprived eye); however, these cells were equal in number to that found in the split brain controls. In the monocularly deprived control cats a relation of 3.2 was found between cells driven by the non-deprived and the deprived eye. Visual disuse, therefore, resulting from monocular deprivation, affects cortical cells under complete absence of binocular competition but is greatly enhanced by the latter.     

Monocular and binocular optic inputs to salamander pretectal neurons: intracellular recording and HRP labelling study

Intracellular recordings and horseradish peroxidase injections were performed in the pretectum and adjacent tegmentum of Salamandra salamandra, while both optic nerves were electrically stimulated. In approximately half of the recorded units no spikes could be evoked but rather graded postsynaptic potentials. The latter type morphologically showed features of interneurons. From a total of 48 recorded units, nearly 60% were excited only by the contralateral optic nerve, whereas approximately 40% were binocular. For the most part (10/19) the binocular cells were excited by the contralateral and inhibited by the ipsilateral optic nerve. Fewer neurons (7/19) received excitatory inputs from both optic nerves. The latency distribution of the monocular cells shows a maximum of 20-30 ms. The same maximum exists for the contralateral inputs to the binocular cells, whereas the ipsilateral inputs to these units were nearly as frequent with latencies of 20-30 and 40-50 ms. Since neurons with the short ipsilateral latencies always had parts of their dendrites within the ipsilateral ocular projection field, a feature which was lacking in the cells with long ipsilateral latencies, it is possible that the longer latencies are due to indirect ipsilateral inputs. Efferents of labelled dorsal pretectal cells reach the contralateral pretectum via the posterior commissure, the basal optic neuropil of the accessory optic system and the tegmental white substance. More ventrally located cells often reach the pretectal and the basal optic neuropil with their dendrites. Axons of this type descend to the medulla oblongata via the medial longitudinal fasciculus.     

Monocular deprivation affects neuron size in the ectostriatum of the zebra finch brain

The effects of different periods of monocular deprivation on cell sizes in the ectostriatum, the telencephalic relay of the tectofugal pathway in zebra finches, were evaluated. Following 20 days of monocular closure, neurons in the deprived and undeprived hemisphere show an unselective hypertrophy of 10%. Extending the deprivation period results in a shrinkage of neurons of the deprived side to values of adult normally reared birds, whereas the non-deprived neurons maintain their hypertrophied size.     

Monocular visual deprivation at the critical period modulates photic evoked responses

Photic evoked responses were recorded from the striate cortex of Long-Evens hooded normal (control) rats and from monocular visual deprivation (MD) rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provide comparison between the contralateral and the ipsilateral striate cortex with relation to the monocular deprived eye. The AVER recorded following binocular photic stimulation after 1 month of monocular deprivation demonstrated that the two visual cortexes responded differently. In the contralsteral hemisphere of the visual cortex (related to the MD eye), allthree components (P2, N2 and P3) of the AVER of the MD rats had significant increases M their peak amplitude as compared to the control recordings. In the ipsilateral cortex, the amplitude of component p2 and N2 was significantly reduced as a result of 1 month of MD. Comparing the AVER amplitudes of the two homotopic sites of the visual cortex obtained from the control group reveals no differences between the two hemispheres but markedly significant differences In P2, N2 and P3 components for the MD group. Based on the literature, the possibility that the monocular visual deprivation at the critical period in early developmental stage modulates the AVER as a result from the neurocytolopical alteration from ailering of GABA and ACh within the striate cortex was discussed. In conclusion, the AVER is a reliable and practical method for studying the effects of monocular deprivation and neuroplasticity in the rat visual cortex.     

Recovery of binocular responses after brief monocular deprivation in kittens

Monocular deprivation induces a rapid ocular dominance change in the developing visual cortex. The early phase of the change is supposed to be labile and stabilized later by consolidation processes. To test the stability of early ocular dominance change, we examined whether binocular responses of cortical neurons can recover after a brief monocular deprivation in anesthetized and paralyzed kittens in which ocular dominance plasticity does not operate. After the 24-h monocular deprivation, most cortical neurons lost their responses to the deprived eye. The deprived eye responses, however, recovered following 2-3 days interval under anesthetized and paralyzed conditions. Visual stimulation did not facilitate the recovery. These results suggest that the early phase of ocular dominance plasticity is labile and declines passively.     

Monocular deprivation alters the development of synaptic structure in the ectostriatum of the zebra finch

The effects of monocular deprivation, beginning at hatching, were examined in the neuropil of ectostriatum, a visual telencephalic projection area in birds. The volume of ectostriatum, the number of synapses and subsynaptic features like the presynaptic terminal size and the length of the postsynaptic contact zone were quantified in juvenile (20 d) and adult (100 d) zebra finches. Monocular deprivation affects almost all of the parameters mentioned above in juvenile birds, but only one (i.e., the size of presynaptic terminals) is permanently altered in adulthood. Both hemispheres are affected in juvenile birds with respect to the volume of ectostriatum, the length of synaptic contact zones and the presynaptic terminal size when compared to normal values. In normal birds the number of synaptic contacts is established at 20 days and remains fairly constant at 100 days. In experimental birds there is an increase in synapse number during this time period. However, no interhemispheric differences or differences compared to normal animals could be identified. The presynaptic terminals in experimental birds are smaller compared to normal values in young (25% for the deprived side; 19% for the non-deprived side) and adult (13% for the deprived side; 11% for the non-deprived side) animals. The only permanent effect caused by monocular deprivation in the ectostriatum is characterized by smaller presynaptic terminals. It is surprising that the tectofugal pathway that is believed to be mostly ipsilateral is not very vulnerable to monocular deprivation in adult animals. It is even more surprising that the deprivation effects are seen on both sides of the brain. The implications of this plasticity will be discussed in this paper.     

Monocular deprivation enhances the nuclear signalling of extracellular signal-regulated kinase in the developing visual cortex

Monocular deprivation (MD) of vision leads to a loss of cortical response to the deprived eye in the early postnatal period (ocular dominance plasticity). The activity of several signal molecules, including extracellular signal-regulated kinase (ERK), has been reported as playing a crucial role in the ocular dominance plasticity. Although pharmacological inhibition of ERK disturbed the ocular dominance plasticity, it remains to be elucidated how the ERK activity is modulated by MD. We herein report the effects of MD on ERK activation in the visual cortex of young and adult rats. Phosphorylated ERK (pERK)-immunopositive cells are mainly distributed in layers II/III of the visual cortex. Following MD, we found a significant decrease in the density of pERK-immunopositive cells in the cortex receiving deprived-eye inputs in both young and adult animals. The amount of pERK protein also decreased in the input-deprived cortex as revealed by Western blotting. Regarding the subcellular localization of pERK, we found a significant increase in the pERK-immunopositive nucleus following MD in young animals. In these animals, the amount of pERK protein in the nuclear fraction of cortical tissue was significantly increased. No up-regulation of the nuclear pERK was observed in adults or following binocular deprivation. These findings suggest that ERK activation may therefore be regulated by different mechanisms between young and adult animals, and MD during the developing period may thus specifically up-regulate the nuclear signalling of ERK.     

Short periods of concordant binocular vision prevent the development of deprivation amblyopia

Based in part on deprivation studies, it is generally agreed that the development of vision and of the central visual pathways of higher mammals such as cats and primates is experience-dependent. Past deprivation experiments employed periods of exclusively abnormal early visual input. Because of the absence of any normal visual input, such studies indicate only the extremes to which the visual system can change in response to visually driven activity (i.e. its capabilities) rather than provide insight into the role of early visual input in normal development (i.e. what it actually does). We examined the possibility that certain visual input, i.e. normal concordant binocular vision, may be more efficacious than others with respect to its effects on the developing visual system and on vision. On a daily basis, one type of visual input, i.e. normal binocular experience (BE), was pitted against abnormal (monocular exposure, ME) input in order to see if one was more effective. We show that 2 h of daily normal concordant, but not discordant, BE outweighs or protects against as much as 5 h of daily abnormal input to permit the development of normal grating acuity and alignment accuracy in the two eyes. Further, we show that splitting the period of BE into two 1-h periods straddling the period of ME was ineffective, thereby indicating the 2 h of BE each day must be continuous to protect against the development of amblyopia.     

The monocular and binocular subfields of the rat's primary visual cortex: A quantitative morphological approach

Primary visual cortex in the rat was studied by a variety of methods: transsynaptic transport of labelled amino acids, 2-deoxyglucose, and staining for perikarya, myelin, and acetylcholinesterase. The analysis was aided by a computer-controlled television image analyzer. The results obtained with different methods agree with one another in describing the position and extent of the entire primary visual cortex as well as its monocular (medial) and binocular (lateral) subareas.