Monocular Enucleation Research Articles

Severing the intercollicular commissure prevents bilateral disruption of the map of auditory space in the superior colliculi following monocular enucleation

A previous study demonstrated that developmental monocular enucleation resulted in bilateral disruption of the formation of the auditory space map in both superior collculi, even though only one colliculus had been deprived of visual input. The present study found similar map disruption, when monocular enucleation was carried out following the initial emergence of the map at 32 days after birth. The study also investigated the effect of monocular enucleation plus simultaneous transection of the intercollicular commissure (a recognised pathway for communication between the colliculi). Multi-unit responses to free-field auditory stimuli were recorded from both colliculi of the two experimental groups. In the group which had later monocular enucleation alone, the auditory responses were disrupted in a manner very similar to those recorded from animals which had undergone early monocular enucleation. Similarly, in the group in which the collicular commissure had been severed at the time of monocular enucleation, the auditory responses were also disrupted in the colliculus contralateral to the enucleation. In contrast, the colliculus ipsilateral to the enucleation exhibited normal, topographically organised, auditory responses. Thus, severing the intercollicular commissure at the time of monocular enucleation protected the map of auditory space in the ipsilateral colliculus.

Intrinsic Variability of Ocular Dominance Column Periodicity in Normal Macaque Monkeys

Little is known about intrinsic variation from animal to animal in the periodicity of columnar systems within various regions of the mammalian cerebral cortex. To address this issue, complete mosaics of the ocular dominance columns were reconstructed from flat-mounts of the left and right striate cortex (V1) in six normal adult macaques (Macaca fascicularis). To identify the columns, we enucleated the right eye and subsequently processed striate cortex for cytochrome oxidase (CO) activity. Average column areas for the intact eye and the missing eye were nearly equal, confirming that monocular enucleation in adult macaques produces negligible column shrinkage. The contralateral eye's columns occupied more territory than the ipsilateral eye's columns, even in the central visual field representation (0 degree to 8 degrees), where they predominated by 52 to 48%. The column mosaics showed remarkable variation in periodicity. The number of column pairs along the V1/V2 border ranged from 101 sets in one monkey to 154 sets in another. Average column width along the V1/V2 border ranged between 670 and 395 microns, a nearly twofold difference. The widest columns were found in the foveal representation. This high degree of innate variability should be taken into account when considering the effects of various sensory manipulations (e.g., strabismus, anisometropia), which have been reported to alter the periodicity of ocular dominance columns. We found pronounced intrinsic variation in the width and number of ocular dominance columns in a sample of six M. fascicularis, indicating that the number of hypercolumns within a given cortical area can range widely among normal members of the same species.

Unilateral eyeball enucleation differentially alters AMPA-, NMDA- and kainate glutamate receptor binding in the newborn rat brain

The aim of the present work was to evaluate the neurochemical effects of early unilateral visual deprivation as a model of impaired visual maturation. For this purpose, binding to the different ionotropic glutamate receptor subtypes was quantified in vision-related and vision-unrelated brain structures of control and unilaterally deprived newborn rats. At post-natal (PN) day 10, male Sprague-Dawley rats underwent either unilateral eyeball enucleation (enucleation group, n = 12) or sham operation (control group, n = 12). In each group, brains were obtained either post-natal day 20 ( n = 6) or post-natal day 30 ( n = 6) and processed for quantitative in vitro autoradiography selective for NMDA, kainate, and AMPA glutamate-binding sites, as well as for the presynaptic adenosine A1 receptor as a control of the deafferentation efficacy. In control animals, quantitative autoradiography revealed an increase in NMDA (e.g. +45% in superior colliculus) and kainate receptor binding (e.g. +55% in visual cortex, layer IV) from post-natal day 20 to post-natal day 30, associated with stable levels of AMPA receptor binding, in the vision-related structures. In the deafferented visual structures, monocular enucleation induces a marked decrease in A1 site density (e.g. −38 to − 52%, in the superficial layer of superior colliculi, at PN day 20 and PN day 30, respectively) in parallel with a mild increase in both NMDA (e.g. + 8 to 9%, in superior colliculi and visual cortex, layer IV at PN day 30, respectively) and AMPA (e.g. +16%, in layer IV of the visual cortex at PN day 30). Superimposed on marked bilateral decreases at PN day 30 in the enucleated rats, kainate receptor binding also revealed a slight but significant decrease (−5%) in the deafferented superior colliculus as compared to the non-deafferented side. The present findings (different time-courses of, and differential effects of deafferentation on, the NMDA, kainate and AMPA glutamate receptor subtypes throughout the visual brain structures) further support the involvement of these receptors in distinctive roles during maturation of the visual system.

Mitochondrial- and nuclear-encoded subunits of cytochrome oxidase in neurons: differences in compartmental distribution, correlation with enzyme activity, and regulation by neuronal activity.

Cytochrome oxidase (CO), a mitochondrial energy-generating enzyme, contains both mitochondrial- and nuclear-encoded subunits. In neurons, local levels of CO activity vary among different neuronal compartments, reflecting local demands for energy. The goals of the present study were to determine if compartmental distribution of CO subunit proteins from the two genomes was correlated with local CO activity, and if their expression was regulated proportionately in neurons. The subcellular distributions of mitochondrial-encoded CO III and nuclear-encoded CO Vb proteins were quantitatively analyzed in mouse cerebellar sections subjected to postembedding immunocytochemistry. Local levels of subunit proteins were also compared to local CO activity, as revealed by CO cytochemistry. In order to study the regulation of subunit protein expression, we assessed changes in immunoreactivity of the two CO subunits as well as changes in CO activity in mouse superior colliculus after 1 to 7 days of monocular enucleation. We found that immunoreaction product for both CO III and CO Vb existed almost exclusively in mitochondria, but their compartmental distributions were different. CO III was nonhomogeneously distributed among different neuronal compartments, where its local level was positively correlated with that of CO activity. In contrast, the subcellular distribution of CO Vb was relatively uniform and did not bear a direct relationship with that of CO activity. Moreover, the two subunit proteins were disproportionately regulated by neuronal activity. CO III and CO activity exhibited parallel decreases after the deprivation of afferent input, and their changes were earlier and to a greater degree than that of CO Vb proteins. Thus, the present findings indicate that the local expression and/or distribution of CO subunit proteins from the two genomes may involve different regulatory mechanisms in neurons. Our data also suggest that the activity-dependent regulation of mitochondrial-encoded CO subunits is likely to play a major role in controlling the local levels of CO content and its activity.

Deafferentation leads to a down-regulation of nitric oxide synthase in the rat visual system

To test the hypothesis that monocular enucleation can cause a decrease in nitric oxide synthase (NOS) in subcortical visual centers, serial sections of superior colliculi and lateral geniculate nuclei from normal and enucleated rats were processed for NOS immunohistochemistry and NADPH-diaphorase histochemistry. Adjacent sections were also reacted for cytochrome oxidase, a metabolic marker, to demonstrate the change in energy demands. We found that both visual centers normally contained moderate levels of NOS, and eye removal caused a consistent down-regulation of NOS, NADPH-diaphorase and cytochrome oxidase on the deprived contralateral side. Optical densitometric values supported these findings ( P < 0.01). Thus, the level and the activity of NOS are regulated by neuronal activity in the rat subcortical visual centers.

The callosal pattern in striate cortex is more patchy in monocularly enucleated albino than pigmented rats

We investigated the effect of neonatal monocular enucleation on the pattern of interhemispheric connections through the corpus callosum in occipital cortex of pigmented and albino rats. Callosal connections were revealed in tangential sections through the flattened cortex following multiple injections of horseradish peroxidase into the opposite hemisphere. In pigmented rats, we found that monocular enucleation induces the development of an anomalous band-like accumulation of callosal connections in middle portions of striate cortex in the hemisphere ipsilateral to the remaining eye, as reported previously. In one-eyed albino rats, we also found callosal connections anomalously placed in middle portions of striate cortex, but they tended to form several patches of labeling rather than a single continuous band as in pigmented rats. Densitometric analysis of the callosal patterns revealed that this difference between rat strains was statistically significant. The increased patchiness in the callosal pattern of one-eyed albino rats may reflect differences in the ipsilateral retinal projections in albino versus pigmented rats.

Demonstration of direct input from the retina to the lateral habenular nucleus in the albino rat

The projection from the retina to the habenular complex was studied using fluorescent retrograde tracers in the albino rat (Wistar, Japan Clea). Following separate unilateral injections of Fluoro-Gold (FG), Fluoro-Ruby (FR), or 4-acetamido,4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS) into the lateral habenular nucleus (LHB), a small population of ganglion cells was labeled sporadically, predominantly those in the nasal retina contralateral to each injection site. Most of them were small cells, ranging from 9 to 16 μm in diameter, roughly corresponding to the type III ganglion cell in the rat retina. Additionally, all of the structures previously described as regions projecting to the LHB were confirmed. Upon re-examination of previous brain sections of albino rats which had undergone monocular enucleation, degenerating retinal nerve axons and/or their terminals, stained by a modified selective silver impregnation method, were observed in the well-documented end regions of retinal afferents as well as the LHB. The degenerating retino-habenular nerve terminals were distributed sparsely and restricted mainly to the caudal part of the LHB contralateral to the side of ocular enucleation. The present experimental data provide evidence for the existence of a non-image forming retino-habenular pathway in the albino rat. We suggest that, besides serving as a point of convergence for some of the major conduction channels of the limbic and striatal systems, the LHB may play more general integrative roles, including participation in the integration of visual information.

Discrimination rerformance and resolution capacity of uncrossed visual pathways in one-eyed albino rats

Our recent study has demonstrated that adult rats with one eye removed at birth (OEB) relearn a discrimination between alternating black and white stripes, 30 mm wide each, oriented horizontally and vertically faster than control rats monocularly enucleated in adulthood (OET), when relearning is carried out after lesions of the visual cortex and transections of the optic tract contralateral to the remaining eye. Yet, we could not obtain the corresponding results in the acquisition of the discrimination following the same surgical treatments: OEBs did master the discrimination, whereas OETs did not. We hypothesized that a large discrepancy in OETs' performance between the acquisition and relearning occurred because the stripes were close to the limit of the resolution capacity of the uncrossed visual pathways (UXVPs), and hence that a better performance of OEBs was to indicate an increase in the resolution capacity, which resulted from reorganization of the UXVPs brought about by monocular enucleation at birth. To test the hypothesis we tried to approximate the limit of the resolution capacity of the UXVPs in OEBs and OETs using seven different sized test stripes ranging from 20 to 5 mm in width after both OEBs and OETs had relearned the discrimination of the 30 mm training stripes following the same surgical treatments mentioned above. It was found that the median width of the smallest stripes for OETs to discriminate was 10 mm, and that of OEBs 7.5 mm. Although OETs could not discriminate the smallest stripes which OEBs could, they were able to discriminate stripes one third smaller than those hypothesized. Based on these findings the possibility was discussed that the acquisition as well as the relearning of the discrimination of the 30 mm stripes mediated by the UXVPs in OEBs and OETs might not be influenced by the resolution capacity, but mostly, if not entirely, by the size of the visual field.

Contrast sensitivity in one-eyed subjects

The effects of early monocular form deprivation on the developing mammalian visual system, and the anatomical and physiological consequences of early monocular enucleation, suggest that the remaining eye of human subjects who had the other eye removed early during development might be capable of supernormal performance. To test this inference, the achromatic contrast sensitivity of the remaining eye of subjects who had the other eye removed at different ages after birth was compared with that of normal subjects tested under monocular and binocular conditions. The results show that all subjects who had an eye removed during early development had a higher contrast sensitivity than the better eye of control subjects. Furthermore, the earlier in development that the eye was removed, the lower the spatial frequency at which contrast sensitivity is enhanced compared with measurements made in the better eye of control subjects, and the larger the range of spatial frequencies over which contrast sensitivity is supernormal.

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.

Neonatal monocular enucleation and the geniculo-cortical system in the golden hamster: shrinkage in dorsal lateral geniculate nucleus and area 17 and the effects on relay cell size and number.

We have examined the effects of neonatal monocular enucleation on the volume of the dorsal lateral geniculate nucleus (dLGN), the area of area 17, and the size and numbers of geniculate relay neurons identified by retrograde transport of HRP from cortex. Compared to values for normal animals, the only significant change contralateral to the remaining eye was an increase in relay cell radius. The effects ipsilateral to the remaining eye were more widespread: we found significant reductions in the volume of the dLGN (27% reduction), the area of striate cortex (22%), and the number (16%) and average soma radius (6%) of geniculate relay neurons. The relay neurons were also more densely packed, suggesting that other geniculate cell types were affected similarly, although this was not explicitly examined. These changes were not uniform throughout the nucleus, and as such, reflected the changes in retinal input. The greatest reduction in cell size occurred in the region of the ipsilateral dLGN receiving the most sparse retinal input subsequent to enucleation. Nor was the shrinkage of the dLGN uniform, being most apparent in the coronal plane especially along the axis orthogonal to the pia; there appeared to be little change in the anteroposterior extent. Shrinkage in area 17 ipsilateral to the remaining eye was the same (about 22%) whether it was defined by myelin staining or transneuronal transport of WGA-HRP. These results show that the transneuronal changes seen in the organization of visual cortex after early monocular enucleation in rodents are associated with only a moderate loss of geniculate relay cells.

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.

Effect of a very early monocular enucleation upon the development of the uncrossed retinofugal pathway in ferrets

Monocular enucleations were done in ferret embryos before or during the earliest stages of development of the retinofugal pathway (E23-E26). The effects on the development of the uncrossed pathway from the surviving eye were assessed on embryonic day 30. This stage was chosen for two reasons: (1) we show that in normal development a substantial uncrossed component from the temporal crescent has developed by E30; and (2) the pathway cannot yet have been affected by the cell death that normally occurs in the retina in the perinatal period. Using DiI labelling from either the temporal crescent or the optic nerve head, we have shown that such early enucleations prevent the formation of the uncrossed pathway from the temporal crescent of the surviving eye. Enucleation at E23/24, before or during the period when the first axons reach the chiasm, prevents the formation of the uncrossed projection. The axons that would normally take an uncrossed course stall lateral to the midline of the optic chiasm. At E26, when many axons have reached the optic chiasm, but none yet come from the temporal crescent, enucleation causes a dramatic reduction in the uncrossed projection, and the complete abolition of the normal uncrossed pathway from the temporal crescent. This demonstrates that there is a requirement for an interaction between the axons of the two eyes at the optic chiasm to establish the normal formation of the uncrossed pathway at the optic chiasm.

Prenatal monocular enucleation induces a selective loss of low-spatial-frequency cortical responses to the remaining eye.

During early development, interactions between the two eyes are critical in the formation of eye-specific domains within the lateral geniculate nucleus and the visual cortex. When monocular enucleation is done early in prenatal life, it induces remarkable anatomical and functional reorganizations of the visual pathways. Behavioral data have shown a loss in sensitivity to low-spatial-frequency gratings in cats. To correlate the behavioral observations with a possible change in the analysis of contrast at the level of primary visual areas we recorded visual evoked potentials at the 17/18 border in two cats enucleated prenatally (gestational age at enucleation, 39-42 days), three neonatal, two control animals, and one animal with a surgical removal of Y-ganglion fibers. Our results show a strong attenuation in the amplitude of response at all contrast values for gratings of low spatial frequency in prenatally enucleated cats, whereas neonatally enucleated and control animals present responses of comparable amplitude. We conclude that the behavioral results reflect the reduced sensitivity for low frequencies of visual cortical neurons. In addition, we define a critical period for the development of the contrast-sensitivity function that seems to be limited to the prenatal gestation period. We suggest that the prenatal interruption of binocular interactions leads to a functional elimination of the Y-ganglion system.

Targeting and activity-related dendritic modification in mammalian retinal ganglion cells

We have studied factors that influence the development of dendritic morphology in hamster retinal ganglion cells. By combining fluorescent retrograde tracing with in vitro Lucifer yellow injection into fixed retina, cells with appropriate and inappropriate visuotopic projections have been compared. In adult hamsters, cells with an aberrant ipsilateral projection from the nasal retina display a uniformly sparse dendritic morphology. However, following monocular enucleation at postnatal day 0 (P0), this population displays a significantly enhanced dendritic complexity in the adult. By contrast, removal of one eye at P6 or at P12 produces progressively less effect. These results suggest that dendritic complement of the adult aberrant projection can be regulated by altering the early postnatal axonal environment. The development of aberrant ganglion cells was investigated to determine the relative influences of cell death and dendritic remodeling in shaping the composition of the adult aberrant population. Aberrant cells were found to be indistinguishable from other cells in nasal retina throughout early development. After ganglion cell death (P1-P12) is over, aberrant cells still display a full range of cell types. However, at eye opening (P16) they undergo a rapid loss of dendritic complexity by remodeling. By P22, aberrant cells display a uniformly sparse dendritic morphology. When hamsters were raised in the dark between P12 (the end of ganglion cell death) and P22, this severe remodeling was blocked. This block was maintained when hamsters were dark reared to P42. Hence, both dark rearing and monocular enucleation at P0 produce similar effects on the development of visuotopically inappropriate hamster retinal ganglion cells. We speculate that the patterns of dendritic sculpting that we have observed reflect activity-mediated modulation of dendritic form via retrograde signals from the terminal arbors. This has implications for retinal ganglion cell morphological classification and, more generally, for mechanisms that influence the dendritic development of other neurons in the CNS.

Transient increase in the in vivo binding of the benzodiazepine antagonist [3H]flumazenil in deafferented visual areas of the adult mouse brain.

Flumazenil is an imidazobenzodiazepine, an antagonist of central benzodiazepine (BDZ) receptors. BDZ binding sites are a modulatory component located on the gamma-aminobutyric acid (GABA) receptor macromolecule. We studied the effect of monocular enucleation on [3H]flumazenil binding in deprived and intact visual areas and nonvisual areas of the adult mouse brain under in vivo conditions. [3H]flumazenil binding was examined at seven time points up to 56 days postenucleation. In some monocularly deprived mice, changes in local blood flow accompanied with the BDZ receptor response were evaluated by coinjection of [3H]flumazenil and 99mTc-HMPAO. Monocular enucleation produced a transient increase in [3H]flumazenil binding in the deprived visual cortex and superior colliculus. At 17 days postenucleation, [3H]flumazenil binding in the anterior and posterior portions of the visual cortex and the superior colliculus increased by 28%, 15% and 23%, respectively, and declined to control levels at 45 days postenucleation. The increase in [3H]flumazenil was accompanied with a decrease in blood flow. Alterations in BDZ receptors and blood flow were selective to deprived visual structures. The regional correlation between the metabolic deficit and the BDZ response provides further support that the increase in BDZ receptor binding is confined to regions of reduced neuronal activity. [11C]flumazenil is an excellent radiotracer for in vivo imaging of benzodiazepine receptors in human brain using positron emission tomography (PET). This study suggests the suitability of [11C]flumazenil for in vivo PET study of BDZ receptor response to deafferentation of visual structures in human brain.

Nuclear-encoded mitochondrial precursor protein: intramitochondrial delivery to dendrites and axon terminals of neurons and regulation by neuronal activity

Mitochondria contain hundreds of proteins, most of which are encoded by the nucleus. In neurons, distal dendrites and axon terminals can be separated from the nucleus by a great distance, and the mechanism by which precursor proteins reach distal neuronal processes is not well understood. While our previous study on cytochrome oxidase suggests a post-translational mechanism of delivery, it is not known whether precursor proteins reach their target processes before or after incorporation into mitochondria. In order to localize only precursor proteins and not the mature form of the subunit in neurons, we generated polyclonal antibodies against synthetic presequence polypeptides specific to nuclear-encoded subunit IV precursor protein of rat brain cytochrome oxidase. We found that the precursors were located not only in neuronal cell bodies, but also in dendrites and axon terminals. This indicates that the conversion of these precursors to their mature form is not confined to the cell body but occurs in dendrites and axons as well. At the electron microscopic level, an overwhelming majority of immunoreaction product was found within mitochondria, suggesting that precursor proteins are transported to neuronal processes mainly within mitochondria, and that their half-lives are much longer in neurons than in yeast and rat hepatocytes. The precursor pool was downregulated in the rat superior colliculus after monocular enucleation, indicating that precursor synthesis and/or degradation is regulated by neuronal functional activity. These results also suggest that local functional demands may play an important role in controlling the processing of precursors and the assembly of holoenzymes in dendrites and axon terminals. This allows neurons to regulate enzyme levels locally, precisely, and rapidly.

Neonatal monocular enucleation-induced cross-modal effects observed in the cortex of adult rat

The cortices of neonatally enucleated rats were explored for somatosensory responses with special reference to an extension into the occipital cortex. Monocular enucleation was performed on rats at birth. The animals were raised and from the age of three months the activity evoked by either electric stimulation of the vibrissa pad or bending of the vibrissae was tested in the contralateral cortex by electric recording and autoradiography. It was found that early enucleation caused an expansion of the somatosensory responses, among others into the visual area. Neurons responsive to visual and somatosen- sory stimuli were demonstrated in the anterior part of the primary and secondary visual areas, contralateral to the enucleation. Electrophysiological and autoradiographic studies unambiguously proved that early enucleation exerted a significant cross-modal effect on the somatosensory responsive area. Abbreviations: LGB, lateral geniculate body; PSTH, post-stimulus time histograms

Effects of chronic monocular enucleation on calcium binding proteins calbindin-D 28k and parvalbumin in the lateral geniculate nucleus of adult rhesus monkeys

The calcium binding proteins parvalbumin and calbindin-D 28k were localized immunocytochemically within the lateral geniculate nucleus of adult monkeys at 1–7 months after monocular enucleation. Within the deafferented magno- and parvocellular layers, parvalbumin and calbindin-D 28k immunoreactive fibers were depleted at all post-enucleation times. The neuronal staining for parvalbumin was similar in numerical density and intensity between the deafferented and intact layers. In hemispheres examined at 5 and 7 months post-enucleation, parvalbumin-immunoreactive fibers were also lost within the deprived ocular dominance bands in layers IVA, IVC and VI of the visual cortex, suggesting that cellular expression or axonal transport of parvalbumin may be decreased in the deafferented geniculate laminae. While the intact magno- and parvocellular layers contained very few neurons that were immunoreactive for calbindin-D 28k, the density of calbindin-D 28k-positive neurons increased in these layers after deafferentation. The counts of calbindin-D 28k and parvalbumin immunostained neurons were not statistically different at 4–7 months post-enucleation. Because virtually all magno- and parvocellular projection neurons express parvalbumin, many parvalbumin neurons that normally do not contain calbindin-D 28k may co-express this in response to injury. The findings suggest that long-term deafferentation imposes additional calcium buffering requirements on lateral geniculate neurons.

Regulation of retinal ganglion cell axon arbor size by target availability: mechanisms of compression and expansion of the retinotectal projection.

The ability of pre- and postsynaptic populations to achieve the proper convergence ratios during development is especially critical in topographically mapped systems such as the retinotectal system. The ratio of retinal ganglion cells to their target cells in the optic tectum can be altered experimentally either by early partial tectal ablation, which results in an orderly compression of near-normal numbers of retinal projections into a smaller tectal area, or by early monocular enucleation, which results in the expansion of a reduced number of axons in a near-normal tectal volume. Our previous studies showed that changes in cell death and synaptic density consequent to these manipulations can account for only a minor component of this compensation for the population mismatch. In this study, we examine other mechanisms of population matching in the hamster retinotectal system. We used an in vitro horseradish peroxidase labeling method to trace individual retinal ganglion cell axons in superior colliculi partially ablated on the day of birth, as well as in colliculi contralateral to a monocular enucleation. We found that individual axon arbors within the partially lesioned tectum occupy a smaller area, with fewer branches and fewer terminal boutons, but preserve a normal bouton density. In contrast, ipsilaterally projecting axon arbors in monocularly enucleated animals occupy a greater area than in the normal condition, with a much larger arbor length and greater number of boutons and branches compared with normal ipsilaterally projecting cells. Alteration of axonal arborization of retinal ganglion cells is the main factor responsible for matching the retinal and tectal cell populations within the tectum. This process conserves normal electrophysiological function over a wide range of convergence ratios and may occur through strict selectivity of tectal cells for their normal number of inputs.