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

Summary The visual representation in the uncrossed retinal projection to the superior colliculus (SC) was examined electrophysiologically by recording multiunit 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° in the ipsilateral visual hemifield to about 40° 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     

The ontogeny of dendrite bundles in rabbit visual cortex

Summary Time schedule and mechanisms of the appearance of dendrite bundles in laminae IV and II/III of the visual cortex have been investigated in the rabbit from the first appearance of the cortical plate during fetal development up to adult stages. Sections cut either perpendicularly or tangentially to the cortical surface were used for light-and electron-microscopic analysis. Dendrite bundles appear during the late fetal period and the first postnatal days in a biphasic process. The first step takes place during late fetal development. Due to migration of neuroblasts along radial processes of glial cells, column-like compartments of neuropil are formed in laminae II–IV which contain the apical processes of the nerve cells situated in deeper layers. They represent the units of origin for the later dendrite bundles. The second step is initiated immediately after birth when axons arrive and small oblique and horizontal dendrites start to sprout from perikarya as well as from the apical dendrites. These new cell processes proliferate and grow rapidly. However, during this growth process groups of apical dendrites of pyramidal cells remain together, and they later form the bundles. In the beginning of this process many apical dendrites are connected with each other by punctae adhaerentiae. The basic pattern of dendrite bundles is present before the eyes open and before the majority of spines and synaptic contacts are formed.     

Effects of neonatal monocular enucleation on the number of GAD-positive puncta in rat visual cortex

Summary Rats that had one eye removed on the day of birth were examined at various postnatal ages with immunocytochemical methods to determine the effect on the development of the GABAergic axonal plexus in the visual cortex. The monocular segment of visual cortex contralateral to the enucleated orbit had 20–30% fewer GABAergic axon terminals than the monocular segment of visual cortex contralateral to the normal eye. Other cortical areas did not show any significant changes. These findings suggest that sensory deprivation of the visual cortex interferes with the normal development of GABAergic neurons.     

Effects of alternating monocular occlusion on the development of visual callosal connections

Summary During normal postnatal development there is a partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. Visual experience early in life can modulate this process. In the present study, we investigated how restricting visual experience to alternating monocular occlusion affects the development of the callosal connections of cortical areas 17 and 18. Alternating monocular occlusion exaggerates the normally occurring partial elimination of immature callosal projections: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum and marginally increases the distribution of these neurons across areas 17 and 18. Examination of these data in the context of the effects of other types of abnormal early visual experience on the corpus callosum and on the anatomy and physiology of areas 17 and 18 indicates that the postnatal development of the corpus callosum is under the control of multiple, interacting influences which differ in the magnitude and quality of their effects. The data also support the conclusion, drawn from our results in prior studies, that normal visual stimulation is necessary for the stabilization of the normal complement of callosal projections.     

Modification of single neurons in the kitten's visual cortex after brief periods of monocular visual experience

Summary Kittens were deprived of form vision by suturing the lids of both eyes, except for a brief period (1, 6 or 20 hours) on the 29th day when the right eye was opened. 6 space and 20 hours of monocular vision produced a distinct shift in the ocular dominance of visual cortical neurons towards the experienced eye, and an increase in the proportion of cells with obvious orientation selectivity. These modifications in the visual cortex were enhanced by a period of consolidation: they were somewhat less obvious if recordings were taken immediately after the exposure but were complete 2 days later. Although remarkably little visual experience was needed for these changes, the results contrast with the effects of rearing in an environment of vertical stripes, where only 1 hour of exposure produces much more striking effects. A normal visual environment may have a less powerful organizing influence on cortical neurons than such an environment containing only one orientation.On leave from Department of Psychology, Pomona College, Claremont, California 91711 (USA).     

Quantitative morphological effects of dark-rearing and light exposure on the synaptic connectivity of layer 4 in the rat visual cortex (area 17)

Summary The quantitative effects of dark-rearing and light exposure on the ultrastructural characteristics of synapses and synaptic boutons in layer 4 of the rat visual cortex (area 17) have been investigated using stereological techniques. Two experimental groups (each containing 5 animals) were investigated i) animals dark-reared upto weaning at 21 days post natum (21DPN) and then light exposed until 52DPN (Group 21/31), and ii) littermate animals totally dark-reared until 52DPN (Group 52dD). The results indicate a significantly higher mean density of synapses in the neuropil of layer 4 in group 21/31 (3.58×10⁸ · mm^-3) compared with group 52dD (2.68×10⁸ · mm^-3). Although the density per unit volume of synapses with identified asymmetrical synaptic membrane specialisations was not significantly different in group 21/31 than in group 52dD (but was significantly lower than animals reared normally), the density of synapses with identified symmetrical synaptic membrane specialisations was about 200% higher in group 21/31 versus group 52dD. However, significant differences were detected in the number of asymmetrical synapses established by single synaptic boutons in group 21/31 (1.21 ± 0.11) compared with group 52dD (1.10 ± 0.09). On the basis of the numbers of post-synaptic targets contacted by an individual synaptic bouton, a significantly higher density of synaptic boutons was found in group 21/31 (2.32×10⁸ · mm^-3) compared with group 52dD (1.82×10⁸ · mm^-3). Furthermore, planar quantitative data indicated significant inter-group differences in the ultrastructure of asymmetrical and symmetrical synaptic boutons. The results of this study provide evidence indicating marked structural alterations in the synaptic connectivity of layer 4 of the rat visual cortex following the light exposure of rats dark-reared upto weaning. Indeed visual deprivation severely affected the inhibitory circuitry in the major thalamorecipient territory of the visual cortex.     

Morphological characteristics of neocortical laminae when studied in tangential semithin sections through the visual cortex of the rabbit

Summary In semithin sections cut tangentially with respect to the surface of the cerebral cortex and with a side length of at most a few mm, it is extremely difficult to be certain which lamina has been sectioned, for instance lamina III or upper lamina IV. In order to provide criteria to overcome this difficulty, a systematic study was carried out in which 1 m semithin sections through the visual cortex of the rabbit were cut in both the frontal and tangential planes and compared with 8–12 m paraffin sections stained for cells and/or myelin.It was found that the arrangement of thick dendrites, of myelinated fibres and of unmyelinated profiles which may be either dendrites or neurites, permits subdivision of the visual cortex into three characteristic horizontal zones which are termed zones A, B and C. The relation between these three zones and the cytoarchitectonic pattern is as follows: Zone A corresponds to the cytoarchitectonic lamina I; zone B comprises lamina II/III, lamina IV and the upper half of lamina V; zone C corresponds to the lower half of lamina V and all of lamina VI. Zones A and B can further be subdivided: Zone A consists of two layers, whereas zone B can be divided into three tiers, each of which is characterized by a particular arrangement of the myelinated and unmyelinated profiles.It is shown that the morphological criteria thus obtained facilitate orientation in tangentially cut semithin sections.     

Failure to find luxotonic responses for single units in visual cortex of the rabbit

Summary The firing frequency of a population of 213 units in striate and circumstriate cortex of the moderately restrained rabbit was studied under the influence of alternating 1-min periods of darkness versus steady, diffuse, featureless illumination. The intent was to determine whether luxotonic responses, so prominent in striate cortex of primates, are indeed absent in rabbits. Such was the case, there being only transient occurrences in three units where the continuing rate of discharge in darkness was double that in the light. There were, however, much more modest differences in rate of continuing discharge in light versus darkness, and for 46% of the units discharging > 1/s this difference exceeded 10% and/or 1/s. The rate of discharge in any case did not provide a reliable index as to the characteristics of a unit's receptive field in response to patterned visual stimuli. The nature and function of luxotonic activity in primates still not being understood, it cannot be decided whether its absence in rabbits represents a true qualitative or merely a quantitative difference between species.Supported by Grant NS 03606 and Contract 70-2279 from the National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of HealthDeceased November 5, 1978     

Cross-modal plasticity after monocular enucleation of the adult rabbit

The mature brain undergoes compensatory reorganization of the primary visual cortex (V1) in response to retinal lesions. This study demonstrates that V1 also supports cross-modal reorganization by observing an increase in tactile responses in V1 after monocular enucleation of the adult rabbit. The proportion of tactile-responsive V1 neurons increased from 0% to 31%, in an area of cortex equivalent to 40 degrees of visual space. Retrograde fiber-tracing analysis suggests that intracortical connections from association areas may underlie these novel responses. Cortical plasticity of this kind may be involved in recovery from sensory system damage and could provide an enhanced sense of touch to the blind.     

Developmental changes of calcium currents in the visual cortex of the cat

Summary During a critical period of postnatal development the visual cortex of kittens is susceptible to experience-dependent modifications of neuronal response properties. Evidence is accumulating that these modifications are triggered by a transient neuronal calcium (Ca) influx. To further investigate this issue we measured extracellular Ca concentrations with ion-sensitive microelectrodes and compared the magnitude and the distribution of stimulus-evoked Ca fluxes in slices of the visual cortex of 4- to 5-week-old kittens and of 6-month-old adult cats. Stimulation of the white matter at 15 Hz for 8 s caused transient decreases of the extracellular Ca concentration ( Ca⁰) in slices of both age groups and in all cortical layers. However, there were developmental changes in the laminar distribution of the Ca⁰: in kittens, they were maximal in layer IV whereas in adult cats they were most pronounced in the supragranular layers. The ratios between the amplitudes of Ca⁰ in layer IV and the supragranular layers were 1.65 ± 0.26 in kittens and 0.43 ± 0.2 in adult cats. These changes in laminar distribution resemble the laminar specific decay of neuronal malleability and parallel the developmental redistribution of 1,4-Dihydropyridine-sensitive Ca channels. Because of these correlations we interpret our findings as support for the hypothesis that experience-dependent modifications are triggered by Ca influx.     

The quantitative effects of dark-rearing and light exposure on the laminar composition and depth distribution of neurons and glia in the visual cortex (area 17) of the rat

Summary The effects of dark-rearing and light-exposure on the distribution of neurons and glial cells types in the rat visual cortex (area 17) have been investigated. Three groups of animals were studied: i) rats reared in the dark until weaning at 21 days post natum (21 DPN) and subsequently light-exposed for 31 days (Group 21/31); ii) rats darkreared until 52 DPN and then exposed to light for 3 days (Group 3 dL); and iii) rats totally dark-reared until 52 DPN (Group 52 dD). Semithin sections tangential to the pial surface were obtained at sampling intervals 50 m apart throughout the depth of the left visual cortex. The volume numerical densities of neurons, astroglia, oligodendroglia, and microglia, at each sampling strata in the cortex were calculated using stereological techniques. The laminer density and distribution of neurons was not significantly different between the three groups. In comparison with group 21/31 there was a marked reduction in the densities of astroglia, oligodendroglia, and microglia in lower layer 5 of groups 3 dL and 52 dD. Additionally, the density of microglia in thalamorecipeint layer 4 was greatly increased in group 3 dL compared with groups 21/31 and 52 dD. These results indicate specific alterations in the glial cell composition of the rat visual cortex following periods of dark-rearing and light-exposure. Furthermore, changes in the density of glial cells in layer 5 may reflect functional modifications in neurons projecting to the superior colliculus.     

An attempt to assess the effects of monocular deprivation and strabismus on synaptic efficiency in the kitten's visual cortex

Summary The relative effectiveness of the two eyes in exciting cells in the visual cortex was assessed, using both natural stimulation and electrical stimulation of the optic discs. It is argued that supramaximal electrical stimulation of the optic nerve could possibly reveal subliminal synaptic inputs even after monocular deprivation or artificial strabismus has caused a loss of natural input from that eye, if such silent synaptic input still survives. However, in kittens monocularly deprived for various periods of time or made artificially strabismic, there was usually excellent agreement between the relative visual excitability in the two eyes and their relative electrical excitability. In one animal, monocularly deprived continuously until 23 weeks of age, we examined the effect of reversibly turning off signals from the normal eye by pressure blinding. There was no evidence of a very rapid return of sensitivity to either electrical or natural stimulation of the deprived eye.Royal Society Locke Research FellowOn leave from The Neurobiology Unit, The Hebrew University of Jerusalem, Jerusalem, Israel     

Shortage of binocular cells in area 17 of visual cortex in cats with congenital strabismus

Summary Twenty-nine pigmented offspring of an innately esotropic female cat exhibited varying deficits in the number of binocular cells recorded in area 17 of the visual cortex as compared to 12 normal cats. Misalignment of the two eyes in these cats was found in the awake as well as in the paralysed state. Pupillography combined with measurements of visual disparity yielded abnormal esotropia of up to 8.4° under paralysis, which corresponds to an abnormal convergence of the freely moving eyes of up to 14° (average 7.4°). In the majority of animals cortical binocularity was found reduced by the two eyes controlling independent sets of separate units (U-shaped ocular dominance distribution) whereas in 7 cats the reduction was due to a partial loss of one eye's influence. The proportion of monocular units correlated with the degree of crossover of the visual axes (r = 0.73). Anatomical investigation of the retinofugal projections revealed normal appearance in three previously recorded cats in which more than 50% of cortical units had been monocularly driven. The small angles of esotropia and the normal appearance of eye position judged by the pupillary positions in the orbit of these cats, might suggest that we found an animal model for microstrabismus.     

Development of the rabbit retina

Summary Measures of rabbit eyes and retinal whole-mounts were used to evaluate the development of retinal area and shape. The retina is shown to have a horizontal axis about a third longer than the vertical axis just before birth, and to adopt an almost symmetrical shape during postnatal development to adulthood. In general, retinal thickness is shown to decrease after birth, but differently in particular retinal regions: the reduction is marked in the periphery, and less pronounced in the visual streak. As an exception, the myelinated region — after it becomes really myelinated, from 9 days p.p. — even increases in thickness. In all regions of the retina, the absolute and relative thickness of the nuclear layers decreases, whereas the relative thickness of plexiform and fibrous layers increases. Proliferation of cells within the rabbit retina was studied during the first three postnatal weeks. ³H-thymidine incorporation was used to demonstrate DNA synthesis autoradiographically in histological sections as well as in enzymatically isolated retinal cells. A first proliferation phase occurs in the neuroblastic cell layer and ceases shortly after birth in the retinal center, but lasts for about one week in the retinal periphery. We found, however, a few ³H-thymidine-labeled cells as late as in the third postnatal week.These late-labeled cells were found within the nerve fiber layer and in the inner plexiform layer. The latter cells were shown to express antigens detected by antibodies directed to the intermediate-sized filament protein vimentin, which are known to label Müller cells and neuroepithelial stem cells. This was confirmed in our preparation of enzymatically isolated cells; all cells with autoradiographically labeled nuclei revealed a characteristic elongated morphology typical for Müller radial glia (and also for early neuroepithelial stem cells). ³H-thymidine-labeled cells in the nerve fiber layer were most probably astrocytic. In analogy to the brain, we conclude that the mammalian retina undergoes a series of proliferation phases: first an early phase producing both neurons and glial cells, and then a late phase producing glial cells, e.g., in the nerve fiber layer. Most probably, the late phase within the inner nuclear layer is glial as well, i.e., consists of dividing Müller cells; it cannot be excluded, however, that there may remain some mitotically active stem cells.     

Stimulus dependence of ocular dominance of complex cells in area 17 of the feline visual cortex

Summary Stimulus dependence of ocular dominance of 31 deep-layer complex cells was assessed from detailed monocular directional tuning curves for motion of bar stimuli or fields of static visual noise, in area 17 of normal adult cats, lightly anaesthetised with N₂O/O₂ supplemented with pentobarbitone. Virtually all cells were binocularly driven, with the anticipated ocular dominance distribution. Interocular differences in directional bias and sharpness of directional tuning for noise were observed in eleven cells, whereas preferred direction and sharpness of tuning for bar stimuli were similar for each eye. In the majority of cells (20/31), any differences between noise and bar tuning in one eye were replicated in the other. Ocular dominance of about half the cells (17/31) for noise and for bar motion was similar, or marginally shifted by up to one ocular dominance group. Substantial shifts in ocular dominance were seen in 14 cells — by up to two ocular dominance groups in 12 cells and by up to three ocular dominance groups in two cells. In three cases these shifts involved a reversal of eye dominance. Notwithstanding these changes, there were no obvious trends in shifts of ocular dominance in favour of the ipsilateral or contralateral eye, nor was there any tendency towards increased binocularity for noise.     

An electron microscope study of the organization of the cerebral cortex of the 60 mm rabbit embryo

Summary The embryonic cerebral cortex was examined for signs of a columnar organization. In vertical montages extending from the intermediate lamina to the pia, nerve cells arranged in columns are separated by bundles of radial processes. However, sections tangential to the pial surface revealed little evidence for repeating modular units; bundles of radial processes are not regular in outline, and surrounding groups of cells display little symmetry in their distribution.Tangential processes representing the development of a rudimentary neuropile are present in the marginal lamina and at lower levels of the cortical plate. However, well defined synapses were not seen at this stage of development when proliferation and migration of neuroblasts continues to provide cells to the upper part of the cortical plate. The association of neuroblasts with bundles of radial fibers suggests that these vertical elements serve as preferential pathways for cells migrating to the cortex.     

The effects of short-term occlusion therapy on reversal of the anatomical and physiological effects of monocular deprivation in the lateral geniculate nucleus and visual cortex of kittens

Summary The relative efficacy of distributed versus massed reverse occlusion therapy in promoting recovery from the anatomical and physiological effects of monocular deprivation was studied in two experiments performed on kittens raised with one eye occluded from eye-opening until 5 weeks of age. The first experiment explored the effects of different periods (ranging from 0.5 to 4 h) of reverse occlusion imposed daily for 20 days. The second, involving a fixed period of reverse occlusion (20 h), examined recovery with respect to the distribution of that period over a varied number of brief daily sessions. Recovery was assessed in terms of changes in cortical ocular dominance and lateral geniculate cell morphology. Although recovery of both cortical ocular dominance and geniculate cell morphology showed the same overall progression with increasing periods of reverse occlusion, changes were apparent in the lateral geniculate nucleus before changes were evident in cortical ocular dominance. A given period of reverse occlusion was found to be far more effective in promoting recovery when distributed over a number of different exposure sessions than when massed together in just one or two sessions. The data suggest that there is a maximal rate of cortical recovery which is achieved with surprisingly brief daily periods of forced visual exposure of the initially deprived eye.Supported by a grant (78/3589) to D.E.M. and S.G.C. from the National Health and Medical Research Council of Australia     

Modified distribution patterns of responses in rat visual cortex induced by monocular enucleation

Monocular enucleation was performed on rats at birth or on the 8th or 15th day, respectively. The animals were raised and from the age of 3 months the evoked activity was tested in the visual cortex. It was found that monocular enucleation changed the distribution of visually evoked responses. In the right hemisphere (contralateral to the preserved eye) two focuses of evoked potentials appeared with large amplitudes shifted to both sides, towards the lateral and medial borders of the primary visual area. In the left hemisphere the focus of the evoked potentials was shifted slightly laterally and posteriorly. Early enucleation caused an expansion of the somatosensory responses into the visual area. Bimodal neurons (responsive to visual and somatosensory stimuli) were observed in the anterior part of the primary and secondary visual areas contralateral to the enucleation. These changes became moderate with increasing age at which enucleation was performed and were not found in animals enucleated on the 15th day after birth.     

Structural changes in the area striata of the mouse after enucleation

Summary The optic pathways of the mouse have been studied by tracing of degenerating fibers after enucleation and coagulation of the lateral geniculate nucleus. The effects of unilateral enucleation at birth in the contralateral area striata of the mouse have been studied with the Golgi method. The number of spines on three different portions of the apical dendrites of layer V pyramidal cells have been counted in the affected area striata of mice 24 and 48 days old enucleated at birth. The results were compared with the countings obtained in the area striata homolateral to the enucleated side and with controls of the same ages. The results indicated that enucleation produces, through a series of transneuronal changes, significant diminution of the number of spines in the apical dendritic segments located in layer IV. The diminution of dendritic spines is more pronounced in younger animals. Specific variations in the orientation of dendrites of stellate cells with ascending axons have been observed in enucleated animals. The significance of these findings has been discussed suggesting the existence of compensatory mechanisms which affect significantly the intrinsic organization of the area striata.     

The development of non-pyramidal neurons in the visual cortex of the rat

Summary We have studied the maturation of non-pyramidal cells in layers II–VI of the visual cortex of albino rats from birth to maturity, using Golgi-Cox and rapid Golgi preparations. At birth, non-pyramidall cells are sparse, immature and concentrated in the deep part of the cortical plate: their number increases towards the end of the first week but they remain sparse and immature in the upper part of the cortical plate. During the second postnatal week, the number, size and extent of dendritic and axonal branching of these cells undergo considerable increases and the cells become conspicuous in layer IV and apparent in the supragranular layers: this growth spurt occurs just after (and may be related to) the arrival and establishment in the cortex during the second half of the first postnatal week, of extrinsic afferents.During the third postnatal week, most of the cells complete their maturation. At the end of this week, the number of spinous cells is greater and the spine density of some cells is higher than in the adult, falling to adult values during the fourth postnatal week. It is noteworthy that the non-pyramidal cells appear to reach maturity at about the same time in all the layers studied, and at the same time as the pyramidal cells with which they are associated. These observations are not in accord with the prevalent view that non-pyramidal cells complete their differentiation much later than pyramidal cells.