Effects Of Monocular Enucleation Research Articles

Blockade of retinal or cortical activity does not prevent the development of callosal patches normally associated with ocular dominance columns in primary visual cortex.

Callosal patches in primary visual cortex of Long Evans rats, normally associated with ocular dominance columns, emerge by postnatal day 10 (P10), but they do not form in rats monocularly enucleated a few days before P10. We investigated whether we could replicate the results of monocular enucleation by using tetrodotoxin (TTX) to block neural activity in one eye, or in primary visual cortex. Animals received daily intravitreal (P6-P9) or intracortical (P7-P9) injections of TTX, and our physiological evaluation of the efficacy of these injections indicated that the blockade induced by a single injection lasted at least 24h. Four weeks later, the patterns of callosal connections in one hemisphere were revealed after multiple injections of horseradish peroxidase in the other hemisphere. We found that in rats receiving either intravitreal or cortical injections of TTX, the patterns of callosal patches analyzed in tangential sections from the flattened cortex were not significantly different from the pattern in normal rats. Our findings, therefore, suggest that the effects of monocular enucleation on the distribution of callosal connections are not due to the resulting imbalance of afferent ganglion cell activity, and that factors other than neural activity are likely involved.

Parvalbumin-immunoreactive cells in the superior colliculus in dog: distribution, colocalization with GABA, and effect of monocular enucleation.

Parvalbumin (PV) is thought to play a major role in buffering intracellular calcium. We studied the distribution, morphology of PV-immunoreactive (IR) cells, and the effect of enucleation on the PV distribution in the superior colliculus (SC) in dog (Canis familiaris) and compared PV labeling to that of calbindin D28K (CB) and GABA. These cells formed three laminar tiers in the dog SC; 1) the upper superficial gray layer (SGL), 2) the lower optic layer (OL) and the upper intermediate gray layer, and 3) the deep layer. The third tier was not very distinct when compared with the other two tiers. The distribution of PV-IR cells is thus complementary to that of CB-IR tiers. Our present data on the distribution of PV-IR cells within the superficial layers are strikingly different from those in previously studied mammals, which show PV-IR cells within the lower SGL and upper OL. However, there were no distinct differences in distribution within the deep layers compared with that of previously studied mammals. PV-IR cells in the SC varied dramatically in morphology and size, and included round/oval, vertical fusiform, stellate, horizontal and pyriform cells. Two-color immunofluorescence revealed quantitatively that 11.67% of the PV-IR cells colocalized with GABA. Monocular enucleation appeared to have no effect on the distribution of PV-IR cells in the contralateral SC. Similar to CB, these data suggest that retinal projection may not control the expression of PV in the dog SC. These results provide important information for delineating similarities and differences in the neurochemical architecture of the visual system.

Glucose Metabolism in the Visual Structures of Rat Monocularly Deprived by Eyelid Suture after Postnatal Eye Opening

To determine the changes in the visual centers of rats following monocular visual deprivation after postnatal eyelid opening (PEO). Monocular eyelid suture was performed on rats on days 1, 3, 5, 7, 14, and 28 after PEO, and the glucose metabolism was measured 1, 2, 5, and 7 days after the eyelid suture. Ex vivo autoradiography with (14)C- or (18)F-labeled 2-deoxy-D-glucose was carried out. Effects of monocular enucleation or dark rearing were also determined. Monocular eyelid suture did not decrease the glucose metabolism in any contralateral visual structures on day 1 after visual deprivation in the PEO1 or PEO3 lid-sutured rats. However, there was a decrease on day 1 after the eyelid suture in PEO7 and older rats. Similarly, monocular enucleation on PEO1 did not reduce the glucose metabolism in the visual cortex (VC), but enucleation on PEO7 and thereafter did. Eyelid suture on PEO8 following dark rearing until PEO7 did not reduce the glucose metabolism 1 day after suture, but reduced it at 7 days after suture. Glucose metabolism was altered by visual deprivation on PEO7 and thereafter. Five days of visual experience after PEO were required for initiation of visual function in the rat visual system.

Distribution of calretinin in the superficial layers of the mouse superior colliculus: Effect of monocular enucleation

We localized a calcium‐binding protein, calretinin, in the superior colliculus of the mouse and studied the distribution and effect of eye enucleation on the distribution of this protein. Calretinin was localized with immunocytochemistry. A dense plexus of anti‐calretinin‐labeled fibers was found within the superficial layers. The highest density was found in the deep superficial gray layer. Monocular enucleation produced an almost complete reduction of calretinin‐immunoreactive fibers in the superficial layers of the superior colliculus contralateral to the enucleation. Furthermore, many calretinin‐labeled cells appeared in the contralateral superior colliculus. These newly appeared neurons had small oval or round cell bodies. The results demonstrate that calretinin identify unique neuronal sublaminar organizations in the superior colliculus of the mouse. They also suggest that the retinal projection may control in part the content of calretinin in some neurons in the superficial layers of the mouse superior colliculus

Effects of monocular enucleation on receptor binding and innervation pattern of the noradrenergic system in the superior colliculus of the pigmented rat

To examine visual activity-dependent regulation of the central noradrenergic (NAergic) system, we carried out in vitro autoradiography for α 2-, β-adrenergic and NMDA, non-NMDA glutamatergic receptors together with immunohistochemical analysis for dopamine β-hydroxylase in the major central visual structures, including the lateral geniculate nucleus, superior colliculus (SC), and visual cortex of pigmented rats, that had received monocular enucleation. β-Adrenergic receptor ( β-AR) binding in the SC contralateral to the enucleated eye was significantly decreased (82%, P<0.01) following monocular deprivation started at P12 and continued for 2 or 11 weeks. No significant change in β-AR binding was found in other structures examined. The number of varicosities in NAergic fibers was significantly increased following longer enucleation, i.e. for 11 weeks, in the contralateral SC (197%, P<0.001), whereas that in the ipsilateral SC was reduced (75%, P<0.001). Changes in α 2-adrenergic, NMDA, and non-NMDA glutamatergic receptor binding were small in these animals. Changes in neither β-AR binding nor innervation pattern of NAergic fibers were found in one-year-old rats that had received a comparable period of monocular enucleation. Furthermore, neither unilateral ablation of the visual cortex to reduce a different set of major afferents nor neonatal enucleation, which induced anatomical reorganization of the afferents, was found to be effective. These findings suggest that β-AR binding and innervation pattern of NAergic fibers in the SC are modified only when massive imbalance of retinal afferent activity is imposed during a limited period in early postnatal life (i.e. the sensitive period).

Effects of monocular enucleation at birth upon learning of a vertical—horizontal discrimination in hooded rats

Previously we have demonstrated that adult albino rats with one eye removed at birth (OEB) relearn a black—white discrimination faster than those monocularly enucleated at maturity (OET) when relearning is conducted after lesioning of the visual cortex contralateral to the remaining eye (Type A experiment). This faster relearning phenomenon is considered to be one behavioral expression of the functioning of the expanded uncrossed visual pathways (expanded UXVPs) resulting from monocular enucleation at birth. However, neither OEBs nor OETs were able to master the discrimination when the experiment was conducted without previous learning following the same surgical treatment (Type B experiment). We hypothesized that this occurs because the cues to discriminate might be close to the threshold of discrimination for either the normal UXVPs or the expanded UXVPs. In order to gain insight into the hypothesis, the present study was undertaken using hooded rats as subjects which genetically possess larger and presumably more efficient functioning UXVPs. The questions addressed were as follows: 1) Whether or not the UXVPs can mediate a vertical—horizontal discrimination in OEBs and OETs. 2) If they can, is there any difference in the upper limit of discrimination capacity between the normal UXVPs and the expanded UXVPs? Three experiments were carried out. In the Type A experiment OEBs relearned discrimination of the 10-mm stripes [0.44 cycles/degree (c/d)] faster than OETs (Experiment 1), yet in the Type B experiment neither OEBs nor OETs were capable of acquiring that discrimination (Experiment 2). However, they could originally master the discrimination equally well when the width of stripes was broadened to 30 mm (0.15 c/d). And when the width of stripes was systematically reduced thereafter, the width of the smallest stripes for the expanded UXVPs to discriminate was found to be 6 mm (0.73 c/d) and that for the normal UXVPs 10 mm (0.44 c/d) [Experiment 3]. These findings were discussed in relation to the hypothesis advanced on our previous data in albino rats.

Postnatal changes in the uncrossed retinal projection of pigmented and albino syrian hamsters and the effects of monocular enucleation

Anterograde and retrograde tracing techniques have been used to study the uncrossed retinal projection in neonatal pigmented and albino Syrian hamsters. The total number of retinal ganglion cells projecting ipsilaterally peaks at postnatal days 2-4 (P2-P4) and declines to adult values by P12. The change in cell numbers has a similar time course in albino and pigmented animals. Although the population of uncrossed cells in the temporal retina of albino hamsters is always less than that in pigmented hamsters, no difference between the colour phases was found for the population of uncrossed cells in nasal retina. Differential cell death also contributes to the adult albino decussation pattern in hamsters: The relative loss of cells from temporal retina in albinos (72%) is greater than that in pigmented animals (56%). The additional loss in albinos does not appear to depend on binocular interactions: The same proportion (30%) of uncrossed cells is "rescued" from death by neonatal monocular enucleation in both colour phases. Flat-mount preparations showing the distribution of uncrossed fibres reveal that a distinct focus of terminals emerges in rostral superior colliculus, which is topographically appropriate for a binocular mapping, at the peak of uncrossed ganglion cell numbers (P4). Comparison of uncrossed terminal distributions and ganglion cell death reveals considerable refinement of the terminals prior to the main phase of cell death. Monocular enucleations performed some time after birth have a greater effect on uncrossed terminal distributions than on cell death. These observations suggest that independent mechanisms may be involved in the regulation of terminal distributions and of cell numbers in the developing uncrossed retinal pathways.

The effects of monocular enucleation on the representation of auditory space in the superior colliculus of the guinea-pig

Multi-unit responses, to free-field auditory stimuli, in the superior colliculus were investigated in guinea-pigs following earlier removal of one eye. Enucleation resulted in disruption of the normal tuning parameter values and of the topographical precision of auditory responses in the SC both ipsilateral and contralateral to the enucleated eye. These data demonstrate that monocular enucleation prevents the normal development of the superior collicular auditory space map.

The effects of monocular enucleation on ganglion cell number and terminal distribution in the ferret's retinal pathway.

Anterograde and retrograde tracing techniques were used to examine the effects of removing one eye at birth on the remaining uncrossed retinal pathway in adult ferrets. After enucleation, the adult number of labelled ganglion cells projecting ipsilaterally changed from an average of 6068 in normal pigmented ferrets to an average of 7813 (29% increase) in pigmented enucleates. The change in albino ferrets was from 1455 in normals to 2319 in enucleates (59% increase). Labelled cells scattered across nasal retina accounted for over half the increase in the uncrossed population. After neonatal enucleation, the volume of lateral geniculate nucleus occupied by the uncrossed projection increased substantially: five-fold in pigmented animals and 20-fold in albinos. These results suggest that neonatal removal of one eye has a greater effect on the distribution of uncrossed terminals than on the survival of uncrossed ganglion cells. There was also an increase in the total number of axons in the surviving optic nerve of both pigmented and albino ferrets (93,000 in enucleates compared with 79,000 in normal animals), which cannot be simply explained as a disruption of binocular competition.

The effects of monocular enucleation on visual topography in area 17 in the rabbit.

The effects of neonatal monocular enucleation on the topographic representation of the ipsilateral visual field in the visual cortex of the rabbit were investigated, using electrophysiological recordings of multi-unit activity in area 17. Topography of receptive fields was determined in normal adult rabbits, adult rabbits monocularly enucleated on the day of birth and adult rabbits monocularly enucleated as adults. In normal rabbits and in adult enucleates, the projection from the ipsilateral eye is represented by a strip of cortex extending approximately 2 mm from the 17/18 border. In neonatal enucleates, the width of the area of cortex in which the projection from the ipsilateral eye is represented was approximately twice as large as normal. Visual topography was normal in the superior-inferior axis but was distorted in the nasotemporal axis. Our data suggest that the abnormal topography observed in the visual cortex of neonatally enucleated rabbits may play a major role in shaping the abnormal visual callosal projections observed in these animals. In addition, our data indicate that, following neonatal monocular enucleation, developmental abnormalities in the topography of geniculocortical projections can occur independently of any alteration in the retinogeniculate projection patterns.

Effect of monocular enucleation or impulse blockage on gamma-aminobutyric acid and cytochrome oxidase levels in neurons of the adult cat lateral geniculate nucleus

Much attention has been paid to the effect of various types of neonatally induced retinal insults on neurons of the cat lateral geniculate nucleus (LGN). Little is known about cellular adjustment to functional alterations commencing in the adult. The present study was aimed at examining the effect of monocular enucleation or retinal impulse blockade on mature neurons of the cat LGN and perigeniculate nucleus. In addition to labeling the relay neurons with cytochrome oxidase (CO) histochemistry and immunohistochemistry, and presumed interneurons with GABA immunohistochemistry, the two markers were also combined in the same section. The results showed that GABA-immunoreactive neurons in the LGN can be subdivided into two major groups: highly immunoreactive neurons (Hir) and moderately immunoreactive neurons (Mir). These two groups differed slightly in their size and CO levels. With monocular enucleation or TTX treatment, there was a reduction in the numerical density of Hir and a concomitant increase in Mir in the affected laminae. However, there was no evidence of a reduction in GABA immunoreactivity in neurons of the perigeniculate nucleus. With regard to relay cells our data were in agreement with our previous findings (Kageyama & Wong-Riley, 1985) that there was a statistically significant positive correlation between cell size and CO levels, so that neurons with large cross-sectional areas were predominately darkly reactive for CO (DCO), while medium-to-small neurons were mainly moderate to lightly reactive (M/LCO). After monocular enucleation or TTX injections, the numerical density and size of DCO were significantly reduced, while those of M/LCO were proportionally increased in the affected laminae, indicating a conversion of some DCO to M/LCO. The results indicate that the maintenance of CO levels in predominately the large relay cells and GABA levels in a subclass of small neurons of the mature cat LGN are activity-dependent and are highly sensitive to retinal insults.

Opioid receptors in the accessory optic system of the rat: Effects of monocular enucleation

The presence and concentrations of each of the three subtypes of opioid receptors (mu, kappa, and delta) has been studied in the accessory optic nuclei (dorsal, lateral, and medial terminal nuclei and the interstitial nucleus of the superior fasciculus, posterior fibers: DTN, LTN, MTN, and inSFp) in normal young rats with radioligands directed towards each opioid receptor subtype. The changes in mu opioid receptors have also been investigated in monocularly enucleated rats in which one eye was removed and the rats sacrificed at postoperative day (PO) 2, 3, 5, 7, 14, and 30. As the MTN is the only accessory optic nucleus of the rat large enough for semiquantitative evaluation, the mu receptor population of the MTN has been subjected to optical microdensitometric analysis. All four of the accessory optic nuclei (AOS nuclei) are found to contain exceedingly high levels of mu opioid receptor binding with the selective radioligand [3H]-[D-Ala,MePhe4, Gly-ol5] (DAGO), low levels of kappa opioid receptor binding using the radioligand [3H]-[ethylketocyclazocine] (EKC) together with the competing agents [D-Pro4]-morphiceptin and [D-Ser2,Thr6]-Leu-enkephalin, and an absence of delta opioid receptor binding with the radioligand [3H]-[D-Ala2,D-Leu5]-enkephalin (DADLE) combined with the competing agent [D-Pro4]-morphiceptin. Monocular enucleation, as studied on the mu opioid receptor population with this experimental approach, results in virtually a complete loss of mu opioid receptors throughout all four of the contralaterally located AOS nuclei, including both dorsal and ventral subdivisions of the medial terminal nucleus (MTNd,v). Kappa and delta receptors are very few (kappa receptors) or are lacking (delta receptors) in the AOS nuclei, and for this reason, the effects of monocular enucleation on these two opioid receptor subtypes have not been investigated. Monocular enucleation also produces a significant lowering in mu receptor binding in other primary optic nuclei (the lateral geniculate nuclei, nucleus of the optic tract, and superficial layers of the superior colliculus) and in the pars principalis of the medial geniculate nucleus (description of changes in mu receptors in non-accessory optic primary optic nuclei will be considered elsewhere). Microdensitometric study of the MTNd,v shows that the decreased binding of mu receptors in this nucleus is barely detectable (about 6%) at PO2 and rises to 6-15% at PO3. At PO5 receptor loss reaches approximately 62%, whereas at PO7 it is about 81% complete. At PO14 and PO30, the mu receptor loss is nearly complete at around 93%.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of monocular enucleation, tetrodotoxin, and lid suture on cytochrome-oxidase reactivity in supragranular puffs of adult macaque striate cortex

The laminar structure and cellular distribution of cytochrome-oxidase (CO) reactivity in supragranular puffs of striate cortex was examined in adult macaque monkeys surviving various periods of monocular enucleation, lid suture, and retinal impulse blockage with tetrodotoxin (TTX). Enucleation and TTX produced a rapid and severe loss in the size of the CO reactive region in puffs dominated by the removed or treated eye compared to slower and less marked reductions obtained in deprived puffs of lid-sutured monkeys. In all deprived animals, the cross-sectional areas of deprived puffs decreased most rapidly in the upper layers (2 and 3A). In long-term enucleated (60 wks) and TTX-treated (4 wks) monkeys, puff area was severely reduced in layer 3B, while reactivity in layer 3B appeared partially spared in lid-sutured monkeys. The density of the CO reaction product was significantly and evenly reduced throughout deprived puffs for all of the monkeys examined; however, this decrease was less severe in adult monkeys lid-sutured for 11 wks. Although no evidence for cell loss was obtained, all three forms of visual deprivation led to lower counts of neuronal perikarya with high levels of CO reaction product in both deprived puff and interpuff areas. This effect was less marked in the deprived puffs of monkeys lid-sutured for 2.5 and 3 yrs, suggesting recovery of CO activity in some neurons. Neurons in deprived puffs and interpuffs were generally similar in size to those in nondeprived regions, although CO-reactive cells were significantly smaller in the deprived puffs of monkeys enucleated for 28.5 or 60 wks. These results indicate that the metabolic response of neuronal elements in supragranular striate cortex depends upon the nature of the visual deficit. The partial sparing of CO reactivity in deprived puffs of lid-sutured monkeys may reflect the continued transmission of certain types of visual stimuli through a closed eyelid.

Control of cell number in the developing visual system. I. Effects of monocular enucleation

Monocular enucleation of hamsters on the day of birth caused an increase in cellular degeneration and a corresponding loss of cells in the dorsal lateral geniculate nucleus contralateral to the enucleation over the first 12 postnatal days. The superficial layers of the contralateral superior colliculus showed a similar increase in cell degeneration, except rostrally where the remaining ipsilateral projection is found. No changes in degeneration were found in either the ipsi- or contralateral ventral lateral geniculate nuclei, the intermediate and deep layers of the superior colliculus, or in the dorsal lateral geniculate and superficial superior colliculus ipsilateral to the enucleation, even though all were denervated to some degree. The disparities in the incidence of degenerating cells normally seen in the central and peripheral regions of the superior colliculus and dorsal lateral geniculate were preserved following the monocular enucleation. The incidence of degenerating cells in early development correlates well with known alterations in adult cell number. Only major denervations of retinal targets appear to be adequate to produce measurable changes in early cellular degeneration.

Effects of monocular enucleation at different stages of development on the uncrossed retinocollicular projection in the opossum

Pouch young opossums aged from 5 to 34 days underwent unilateral eye enucleation and the projection from the remaining eye to the superior colliculus (SC) was explored at maturity by anatomical and physiological methods. The results were compared to data from normal or adult enucleated animals. Analysis of the experimental group showed that early enucleation resulted in an increased ipsilateral pathway which varied in terminal distribution with the timing of the lesion. When performed in the very young (first and second postnatal week) the uncrossed retinocollicular projection covered the entire area of the superficial layers of the superior colliculus but formed mediolateral bands of high and low label density at the rostral aspects of the SC. In the remainder of the early enucleated group the labeling also covered the entire area of the optic layers but the density of labeling was relatively homogeneous throughout the rostrocaudal extension of the SC. The distribution pattern of the uncrossed projection in adult enucleated opossums was similar to that described previously in normal animals. The electrophysiological results showed that, at all ages examined, early enucleation resulted in an orderly but expanded map in the SC restricted to the sector of the visual field seen by the temporal retina. The different anatomical patterns found in animals enucleated at these two early stages of development could not be distinguished by multiunit recordings.

Enucleation demonstrates ocular dominance columns in Old World macaque but not in New World squirrel monkey visual cortex

The effect of monocular enucleation on basophilic and metabolic staining in primary (striate) visual cortex has been compared in Old and New World monkeys. Both species show a 30-40% shrinkage of neurons in the layers of dorsal lateral geniculate nucleus receiving axons from the enucleated eye. In striate cortex Old World macaque monkeys show alternating bands of increased and diminished staining in layers 3, 4 and 6, corresponding to ocular dominance columns. New World squirrel monkeys show staining patterns in all layers which are unchanged from normal cortex, suggesting that New World monkeys lack obvious ocular dominance columns.