Neonatal Monocular Enucleation Research Articles

Cross-hierarchical plasticity of corticofugal projections to dLGN after neonatal monocular enucleation.

Perception is the result of interactions between the sensory periphery, thalamus, and cerebral cortex. Inputs from the retina project to the first‐order dorsal lateral geniculate nucleus (dLGN), which projects to the primary visual cortex (V1). In return, the cortex innervates the thalamus. While layer 6 projections innervate all thalamic nuclei, cortical layer 5 neurons selectively project to the higher order lateral posterior nucleus (LP) and not to dLGN. It has been demonstrated that a subpopulation of layer 5 (Rbp4‐Cre+) projections rewires to dLGN after monocular or binocular enucleation in young postnatal mice. However, the exact cortical regional origin of these projections was not fully determined, and it remained unclear whether these changes persisted into adulthood. In this study, we report gene expression changes observed in the dLGN after monocular enucleation at birth using microarray, qPCR at P6, and in situ hybridization at P8. We report that genes that are normally enriched in dLGN, but not LP during development are preferentially downregulated in dLGN following monocular enucleation. Comparisons with developmental gene expression patters in dLGN suggest more immature and delayed gene expression in enucleated dLGN. Combined tracing and immuno‐histochemical analysis revealed that the induced layer 5 fibers that innervate enucleated dLGN originate from putative primary visual cortex and they retain increased VGluT1+ synapse formation into adulthood. Our results indicate a new form of plasticity when layer 5 driver input takes over the innervation of an originally first‐order thalamic nucleus after early sensory deficit.

The Regulation of Corticofugal Fiber Targeting by Retinal Inputs.

Corticothalamic projection systems arise from 2 main cortical layers. Layer V neurons project exclusively to higher-order thalamic nuclei, while layer VIa fibers project to both first-order and higher-order thalamic nuclei. During early postnatal development, layer VIa and VIb fibers accumulate at the borders of the dorsal lateral geniculate nucleus (dLGN) before they innervate it. After neonatal monocular enucleation or silencing of the early retinal activity, there is premature entry of layer VIa and VIb fibers into the dLGN contralateral to the manipulation. Layer V fibers do not innervate the superficial gray layer of the superior colliculus during the first postnatal week, but also demonstrate premature entry to the contralateral superficial gray layer following neonatal enucleation. Normally, layer V driver projections to the thalamus only innervate higher-order nuclei. Our results demonstrate that removal of retinal input from the dLGN induces cortical layer V projections to aberrantly enter, arborize, and synapse within the first-order dLGN. These results suggest that there is cross-hierarchical corticothalamic plasticity after monocular enucleation. Cross-hierarchical rewiring has been previously demonstrated in the thalamocortical system (Pouchelon et al. 2014), and now we provide evidence for cross-hierarchical corticothalamic rewiring after loss of the peripheral sensory input.

In vivo evaluation of retinal and callosal projections in early postnatal development and plasticity using manganese-enhanced MRI and diffusion tensor imaging

The rodents are an excellent model for understanding the development and plasticity of the visual system. In this study, we explored the feasibility of Mn-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) at 7 T for in vivo and longitudinal assessments of the retinal and callosal pathways in normal neonatal rodent brains and after early postnatal visual impairments. Along the retinal pathways, unilateral intravitreal Mn2+ injection resulted in Mn2+ uptake and transport in normal neonatal visual brains at postnatal days (P) 1, 5 and 10 with faster Mn2+ clearance than the adult brains at P60. The reorganization of retinocollicular projections was also detected by significant Mn2+ enhancement by 2%-10% in the ipsilateral superior colliculus (SC) of normal neonatal rats, normal adult mice and adult rats after neonatal monocular enucleation (ME) but not in normal adult rats or adult rats after monocular deprivation (MD). DTI showed a significantly higher fractional anisotropy (FA) by 21% in the optic nerve projected from the remaining eye of ME rats compared to normal rats at 6 weeks old, likely as a result of the retention of axons from the ipsilaterally uncrossed retinal ganglion cells, whereas the anterior and posterior retinal pathways projected from the enucleated or deprived eyes possessed lower FA after neonatal binocular enucleation (BE), ME and MD by 22%-56%, 18%-46% and 11%-15% respectively compared to normal rats, indicative of neurodegeneration or immaturity of white matter tracts. Along the visual callosal pathways, intracortical Mn2+ injection to the visual cortex of BE rats enhanced a larger projection volume by about 74% in the V1/V2 transition zone of the contralateral hemisphere compared to normal rats, without apparent DTI parametric changes in the splenium of corpus callosum. This suggested an adaptive change in interhemispheric connections and spatial specificity in the visual cortex upon early blindness. The results of this study may help determine the mechanisms of axonal uptake and transport, microstructural reorganization and functional activities in the living visual brains during development, diseases, plasticity and early interventions in a global and longitudinal setting.

Metabolic changes in visual cortex of neonatal monocular enucleated rat: a proton magnetic resonance spectroscopy study

Neonatal monocular enucleation (ME) is often employed to study the developmental mechanisms underlying visual perception and the cross-modal changes in the central nervous system caused by early loss of the visual input. However, underlying biochemical or metabolic mechanisms that accompany the morphological, physiological and behavioral changes after ME are not fully understood. Male Sprague-Dawley rats (N=14) were prepared and divided into 2 groups. The enucleated group (N=8) underwent right ME (right eye removal) at postnatal day 10, while the normal group (N=6) was intact and served as a control. Three weeks after ME, single voxel proton magnetic resonance spectroscopy (1H MRS) was performed over the visual cortex of each hemisphere in all animals with a point-resolved spectroscopy (PRESS) sequence at 7T. The taurine (Tau) and N-acetylaspartate (NAA) levels were found to be significantly lower in the left visual cortex (contralateral to enucleated eye) for enucleated animals. Such metabolic changes measured in vivo likely reflected the cortical degeneration associated with the reduction of neurons, axon terminals and overall neuronal activity. This study also demonstrated that 1H MRS approach has the potential to characterize neonatal ME and other developmental neuroplasticity models noninvasively for the biochemical and metabolic processes involved.

Reorganization of the uncrossed visual pathways as revealed by Fos-like immunoreactivity in rats with neonatal monocular enucleation

To elucidate the neuronal characteristics of the functional expansion in the uncrossed visual pathways (UXVPs), resulting from early monocular enucleation in rats, the feasibility of stimulus-dependent induction of the immediate early gene c-fos was examined immunohistochemically. In the UXVPs of rats with monocular enucleation at birth, patterned visual stimuli induced Fos-like immunoreactive (FLI) neurons much more densely in wide areas of the superficial layer throughout the superior colliculus (SC), and in the striate and extrastriate areas of the visual cortex (VC). In the UXVPs of rats monocularly enucleated after maturity, however, only a few stimulus-dependent FLI neurons were scattered in the restricted portions of the SC and the VC.

Reorganization of the corticotectal projections introduced by neonatal monocular enucleation in the Monodelphis opossum and the influence of serotoninergic depletion

The influence of neonatal serotoninergic lesion (performed with s.c. injection of 5,7-dihydroxytryptamine) on the plasticity of the developing corticotectal projection was studied in the gray short-tailed opossum ( Monodelphis domestica). As a first step, the placement and density of neurons projecting from the visual cortical areas to the superior colliculus was established in the adult opossum. Injections of retrogradely transported fluorescent dyes into the superior colliculus of intact three-month-old animals labeled neurons of cortical layer V. In this species, there are three visual areas: the striate area and two secondary areas, the laterally placed peristriate area and the medial visual area. The population of the labeled neurons was denser in peristriate and medial visual areas than in the striate area. Secondly, the influence of neonatal monocular enucleation on the extent of this projection was investigated, alone or in combination with a serotoninergic lesion. Injection of dyes into the superior colliculi of three-month-old animals that were unilaterally enucleated on the second postnatal day also labeled neurons of cortical layer V. However, the density of the cortical neurons projecting to the superior colliculus contralateral to the remaining eye was much lower. This reduction was most profound in the striate visual area. No significant modifications of this projection were found on the side ipsilateral to the remaining eye. In another group of opossums, unilateral enucleation on the second postnatal day was combined with serotoninergic lesion. Brains of some of the treated pups were immunostained for serotonin on the fifth postnatal day. At this age, 70–80% of serotoninergic axons in the brain were missing. However, in about three weeks these axons had regrown, and their density in the neocortex was approximately the same as in the control animals. We conclude that severe reduction of the serotoninergic innervation during the early postnatal period did not influence the plastic changes induced in the corticotectal projection by unilateral enucleation.

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.

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.

Altered Topography in the Geniculo-cortical Projection of the Golden Hamster Following Neonatal Monocular Enucleation.

The consequence of neonatal eye removal on the adult organization of the geniculo-cortical pathway was studied anatomically in hamsters. Separate discrete injections of rhodamine- and green-fluorescent latex microspheres were made into the primary visual cortex of adult hamsters. The distribution of labelling in the dorsal lateral geniculate nucleus (dLGN) of normal animals was compared with that seen in animals monocularly enucleated at birth. In the normal animals, as expected, the projection has a precise topographic order. This is also true of the projection contralateral to the remaining eye in the enucleated animals. However, on the side ipsilateral to the remaining eye, the visual cortex appears to receive two convergent projections from the deafferented dLGN, one mirroring the other. A single injection made in very lateral cortex labels cells in two discrete regions of the dLGN. As the injection is made progressively more medial, the two patches of labelled cells converge. Eventually, the two patches are no longer discrete so that injections into central area 17 produce just one, extended patch of labelling. These results suggest that the altered retinal input to the dLGN may affect the subsequent development of ordered geniculo-cortical projections.

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.

Functional consequences of modification of callosal connections by perinatal enucleation in rat visual cortex

The effects of neonatal monocular enucleation (right eye) on the callosal connections in the rat visual cortex were studied by physiological and morphological methods. Evoked activity was recorded in the left hemisphere, i.e. contralaterally to the enucleated eye. After enucleation, trans-callosally evoked responses were recorded in a widened stripe of the lateral visual cortex. Compared with the controls, the responsive area was expanded laterally and medially, i.e. into the lateral part of the primary visual area and within the secondary visual cortex (lateral part). Within about 0.5 mm of the expansion, the responses did not differ from those recorded in areas with “normal” callosal connections. Morphological evidence is presented suggesting that this expansion of evoked responses with high amplitudes and short latencies corresponds to an extension of callosal connections with a high density of axon terminals in layers two and three. Further medially within the primary visual cortex, callosally evoked responses with low amplitudes and longer latencies were recorded. The main types of unit responses and characteristic interactions between visually and callosally evoked responses are shown and discussed. These results suggest that following neonatal enucleation (1) the callosal connections expand and form functional synapses in the lateral part of the visual cortex, (2) these connections can activate cortical neurons either directly or by mediation of associational connections between the lateral secondary and primary visual cortex areas and (3) callosal connections can interact with visually evoked potentials and unit responses.

Effects of neonatal monocular and binocular enucleation on transient acetylcholinesterase activity in developing rat visual cortex

Geniculo-recipient layers of visual cortical area 17 in the laboratory rat display a transient pattern of acetylcholinesterase (AChE) activity during the second and third postnatal weeks of life. The appearance of the AChE histochemical reaction product and its distribution in thalamic recipient layers of cortical area 17 suggest that this transient AChE serves as a marker for the region of geniculocortical axon terminals. In the present study, infant rats were enucleated monocularly or binocularly on the day of birth. Animals were sacrificed at postnatal days 5–21. Frozen sections cut in either the transverse plane or parallel to the pial surface were processed for AChE histochemistry. Neonatal monocular enucleation resulted in a marked reduction of transient AChE activity in thalamic recipient layers of the medial part of area 17 contralateral to the enucleated orbit, i.e., the monocular segment of area 17. No loss of AChE was observed in area 17 ipsilateral to the enucleation. Pigmented and albino strains of rats did not differ significantly in the extent to which monocular enucleation reduced the transient AChE in contralateral visual cortex. Neonatal binocular enucleation resulted in an almost complete loss of AChE histochemical staining in thalamic recipient layers throughout cortical area 17, without loss of AChE in other cortical regions. These data support the hypothesis that transient AChE serves as a marker for the region of geniculocortical axon terminals, and also demonstrate that the transient expression of AChE in visual cortex depends upon normal innervation or activity of the geniculocortical neurons.

The effects of neonatal monocular enucleation on the organization of ipsilateral and contralateral retinothalamic projections in the rabbit

Autoradiographic methods were used to compare the ipsilateral and contralateral retinothalamic projections in pigmented Dutch-Belted rabbits that had neonatal monocular enucleation with the projections found in normally reared rabbits. In the normal adult rabbit, there is dense label throughout the dorsal lateral geniculate nucleus (LGd) except for a decreased label density in the region corresponding to the ipsilateral input. Following neonatal monocular enucleation, the contralateral projection fills in the part of the LGd corresponding to the ipsilateral input. Our data indicate that following monocular enucleation, two processes occur: an arrest of the segregation process and an expansion of the contralateral projection into the space normally containing the terminals of the ipsilateral projection. In addition, this filling in of the terminal space occurs relatively rapidly and is completed by day 14. No changes, however, were observed in the ipsilateral projection to the LGd. Unlike the LGd, the ventral lateral geniculate nucleus and the intergeniculate leaflet showed increases in the size of the ipsilateral projection region, and no changes in the contralateral projection. The present findings suggest that there may be different mechanisms governing whether alterations in the distribution of retinothalamic projections will occur in either the ipsilateral or contralateral nucleus.

The effects of prenatal and neonatal monocular enucleation on visual topography in the uncrossed retinal pathway to the rat superior colliculus.

The visual representation in the uncrossed retinal projection to the superior colliculus (SC) was examined electrophysiologically by recording multi-unit responses in paralysed, anaesthetised adult rats (both pigmented and albino), which had been monocularly enucleated either prenatally or soon after birth. This manipulation partially stabilises an exuberant neonatal projection from the remaining eye to the ipsilateral SC. Neuronal responses were also stronger and the multi-unit receptive fields larger than in intact animals. Many of the visual fields recorded on penetrations in caudal SC were located in the peripheral ipsilateral visual hemifield, corresponding to nasal retina. Such receptive fields are not seen in normal animals and were not found in animals enucleated on day 3 or later. The topographic representation of the dorso-ventral retinal axis, lateral to medial in the SC, was normal in all experimental animals. The representation of the naso-temporal retinal axis was abnormal and more variable. In all operated animals as the recording electrode was moved caudally away from the rostral pole of the SC, the corresponding receptive fields moved gradually from up to 40 degrees in the ipsilateral visual hemifield to about 40 degrees into the contralateral hemifield (a location corresponding to the peripheral edge of the temporal retina). This is the mapping polarity found in the normal uncrossed retinal projection. In the enucleated animals, the map was expanded and frequently displayed a clustering of fields arising from far temporal retina. In animals enucleated prenatally or on the day of birth, visual responses could be recorded in more caudal SC. The corresponding receptive fields now moved nasally on the retina, generating reversals in the map. The most caudal penetrations in these early enucleates frequently gave receptive fields located in retina nasal to the optic disc, up to 90 degrees into the ipsilateral visual hemifield. These results demonstrate that a temporal relationship exists between the order and mapping polarity of the visual field in SC and the time of enucleation. Prenatal enucleation produces reversals of the mapping polarity in caudal SC while neonatal enucleation produces an expanded map but one with a mapping polarity appropriate for an uncrossed projection.

Transient patterns of acetylcholinesterase activity in visual cortex of the rat: Normal development and the effects of neonatal monocular enucleation

This paper describes the normal development and disappearance of acetylcholinesterase (AChE) activity in layer IV of rat visual cortex and the effects of neonatal monocular enucleation on this transient pattern of AChE activity. Subjects were laboratory-born male or female Long-Evans rats. Some animals underwent monocular enucleation within 6 h of birth. Animals were sacrificed at various ages and AChE activity was detected histochemically in tissue sections. AChE activity is first detectable histochemically in visual cortex area 17 as a fine fiber-like plexus in layer IV at about 7 postnatal days of age. The intensity of the staining increases during the second postnatal week and reaches peak intensity at days 12–14. The intensity of the AChE staining in layer IV of area 17 appears to decrease during the third postnatal week and the dense AChE band disappears by postnatal day 21. The distribution of AChE in layer IV of area 17 corresponds closely to the field of termination of geniculocortical projections and the fiber-like pattern of AChE activity resembles the appearance of an axonal terminal field. Neonatal monocular enucleation results in a marked decrement in the spatial extent of the AChE activity in layer IV of cortical area 17. The AChE-positive plexus is lost in the medial regions of area 17 contralateral to the enucleated eye. AChE activity remains in the lateral part of area 17, probably corresponding to that part of area 17 innervated by secondary projections from the intact ipsilateral eye. The functional role of this transient AChE activity is unknown. The present data suggest that AChE activity is characteristic of geniculocortical axon terminals during the period of time in which they are establishing functional connections with postsynaptic sites in cortex.

Identification of synapses formed by the aberrant, uncrossed retinogeniculate projection in the hamster after neonatal monocular enucleation.

The terminals of the abnormally enhanced, stabilized uncrossed retinogeniculate projection in adult hamsters produced by removal of one eye at birth, were labelled by injection of HRP into the remaining eye and examined by electron microscopy. Labelled terminals closely resembling normally positioned retinal terminals were found to make well-differentiated synaptic contacts with geniculate projection and interneuron-like cells in regions of the dorsal lateral geniculate nucleus that do not receive uncrossed retinal input in normal adult animals.

The postnatal development of retinocollicular projections in normal hamsters and in hamsters following neonatal monocular enucleation: A horseradish peroxidase tracing study

The pattern of distribution of the retinal projections to the superior colliculus (SC) has been studied in developing normal hamsters and in hamsters following unilateral eye enucleation at birth, using the anterograde horseradish peroxidase (HRP) method. The results show that in normal hamsters the contralateral retinocollicular projection has already reached the caudal pole of the SC on the day of birth, and covered the entire SC by day 1. The ipsilateral retinocollicular projection is distributed only to the rostrolateral portion of the SC on day 0, but has covered the entire area of the SC on day 1. The innervation of the SC by the ipsilateral projection increases gradually until it reaches its maximum density on day 3 or day 4. Beginning on day 6, the density of the ipsilateral projection decreases markedly except in areas where there is a distinct clumping of retinal fibers. The normal adult pattern, which consists of dense clumps of ipsilateral retinal projections in the rostral half of the SC and a sparse ipsilateral retinal projection distributing in almost the entire extent of the SC, is established on day 10. In animals in which one eye was removed on the day of birth, the ipsilateral projection is observed in the rostral two-thirds of the SC on day 1, and innervates the entire extent of the colliculus on day 2. On day 3 or day 4, this projection is denser than that found in normal animals of the same age. The SC remains heavily innervated by ipsilateral fibers on and after day 6. The abnormal adult pattern, which consists of dense ipsilateral retinal projections in most parts of the SC, is observed on day 10. The anomalous ipsilateral retinocollicular projection which develops in eye-enucleated animals suggests that there is a competitive interaction between fibers from the two eyes during development which is critical in shaping the normal adult pattern of the ipsilateral retinocollicular projection. The early development of the contralateral projection is in advance of the ipsilateral projection, and removal of the contralateral fibers by eye enucleation at birth seems to result in a further delay in the development of the ipsilateral projection. This suggests that in the hamster the contralateral fibers may play a role in guiding the ipsilateral fibers to reach their target region. The normal development of the ipsilateral projection can be divided into two phases: there is an initial progressive increase in the density of the projection, followed by a decrease in the extent and, in some regions, the density of the projection. The implies that some of the ipsilateral fibers are transient in nature and are eliminated during development. In unilaterally enucleated hamsters the ipsilateral projection remains substantial after day 6 which suggests that some of the uncrossed fibers which would normally be eliminted are retained. In addition, the absolute extent of the enhanced ipsilateral projections is larger than the absolute extent of the normal projection at its greatest. These observations suggest that rerouting and/or sprouting of the uncrossed retinal fibers may also be important in generating the enlarged projection observed in hamsters with one eye removed at birth.

Bilateral changes in soma size of geniculate relay cells and corticogeniculate cells after neonatal monocular enucleation in rats

Some areas of relay cells of the lateral geniculate nucleus and of corticogeniculate cells of normal rats (n= 4) were compared with those of neonatally unilaterally eye-enucleated adult rats (n= 13). These cells were labeled by retrogradely transported HRP. Monocular enucleation was performed on postnatal days 1 (PND 1) (n= 4), 3 (PND 3), (n= 5) and 6 (PND 6)_(n= 4). The resulsts are summarized as follows. (1) In PND 1 rats soma areas of relay cells were 12–16% smaller than those of normal rats, but only for the geniculate nucleus ipsilateral to the remaining eye. In PND 3 and 6 rats the areal shrinkage of relay cells was 27–39% of the normal control for both hemispheres, though it was less marked in the hemisphere contralateral to the remaining eye. (2) The corticogeniculate cells were distributed in layers V and VI in eye-enucleated rats as well as in normal rats. Soma areas of both layer V and VI cells increased in PND 1 rats for both hemispheres by about 15–47% of the normal control. InPND 3 rats increase in soma size tended to occur for layer VI cells, although the data varied from animal to animal. In summary, it was established that unilateral eye-enucleation in rats at birth induced soma size changes of the geniculate relay cells and of the corticogeniculate cells in the non-deafferented as well as in the deafferented hemisphere. Possible mechanisms for the bilateral changes in soma area of central visual cells after neonatal monocular enucleation are discussed.

Plastic changes in the distribution and soma size of retinal ganglion cells after neonatal monocular enucleation in rats

Using the method of retrograde labeling of ganglion cells with HRP, we studied in adult rats the plastic changes in the retinogeniculate projections due to monocular enucleations shortly after borth. Four normal and 6 neonatally enucleated rats were used. In two of the normal and 4 of the enucleated rats a small amount of HRP was injected into the dorsal lateral geniculate nucleus (LGd) and in 4 other rats massive injections were made into the optic tract near the LGd. Neonatally unilaterallu eye-enucleated rats were characterized by an expanded distribution of ipsilaterally projecting ganglion cells all over the retina of the remaining eye and by a densely packed distribution of these cells in the lower temporal retina in which area these cells have only a moderate density in normal rats. On the contrary, in the lower temporal retina of monocularly enucleated rats the incidence of contralaterally projecting ganglion cells was decreased. Some areas of ipsi- and contralaterally projecting ganglion cells were measured for the peripheral crescent in lower temporal and lower nasal retinas. As compared with normal rats, neonatally enucleated rats had a larger mean soma area of ipsilaterally projecting cells and a smaller mean soma area of contralaterally projecting cells. This result was interpreted as suggesting that after neonatal monocular enucleation medium to large cells had changed their side of axonal projection from the contralateral to ipsilateral LGd.