The effects of panretinal photocoagulation on the primary visual cortex of the adult monkey.

PURPOSE: To determine the effects of panretinal photocoagulation (PRP) on the levels of cytochrome oxidase (CO), Zif268, synaptophysin, and growth-associated protein 43 (GAP-43) in the primary visual cortex of adult monkeys. METHODS: Ten adult primates underwent unilateral argon laser PRP with instrument settings at 300 to 500 microns spot diameter, 200 to 500 mW power intensity, and 0.1 to 0.2 second duration, causing moderate to severe burns in the peripheral retina. At 20 hours, 12 days, 6 months, and 13 months after laser treatment, the visual cortex was assessed histologically for CO and immunohistochemically for Zif268, synaptophysin, and GAP-43. RESULTS: PRP resulted in transneuronal changes in the relative distributions of CO, Zif268, synaptophysin, and GAP-43 in the primary visual cortex. CO activity was relatively decreased in the lasered eye's ocular dominance columns at 12 days post-PRP, with recovery by 13 months post-PRP. The level of Zif268 was dramatically decreased in the lasered eye's ocular dominance columns at 20 hours post-PRP, with gradual recovery by 13 months post-PRP. Levels of synaptophysin and GAP-43 immunoreactivity were increased in both the lasered and the nonlasered eyes' ocular dominance columns at 6 months post-PRP. CONCLUSION: PRP treatment results in metabolic activity changes in the visual cortex of the adult monkey. These changes are followed chronologically by spatial redistribution of synaptophysin and GAP-43, neurochemicals known to play a role in cortical plasticity. This study demonstrates, for the first time, that PRP as used in the treatment of diabetic retinopathy results in a redistribution of neurochemicals in the adult monkey visual cortex. Such changes may help explain the anomalous visual functional loss often reported by patients after PRP.

Axotomy-induced neuronal death and reactive astrogliosis in the lateral geniculate nucleus following a lesion of the visual cortex in the rat.

Following a unilateral lesion of the visual cortex (cortical areas 17, 18, and 18a) in adult rats, neurons in the ipsilateral dorsal lateral geniculate nucleus (LGN) are axotomized, which leads to their atrophy and death. The time course of this neuronal degeneration was studied quantitatively, and the astroglial response was examined with glial fibrillary acidic protein immunohistochemistry. More than 95% of the neurons in the ipsilateral LGN survive during the first 3 days following a lesion of the visual cortex. However, in the next 4 days, massive neuronal death ensues, reducing the number of surviving neurons to approximately 33% of normal by the end of the first postoperative week. Between 2 weeks and 24 weeks postoperatively, the number of neurons present in the LGN declines very gradually from 34% to 17% of normal. Three days after a lesion of the visual cortex, the mean cross-sectional areas of ipsilateral LGN neurons are 13% smaller than normal (87%). By 1 week after the operation, surviving LGN neurons have atrophied to 66% of their normal area. Subsequently, the size of surviving neurons declines slowly to approximately 50% of normal at 24 weeks after the cortical lesion. Astrocytes in the ipsilateral LGN also react to cortical damage. At 1 day after a lesion of the visual cortex, glial fibrillary acidic protein immunoreactivity in the LGN is almost undetectable, but a distinct increase in immunoreactivity is seen at 3 days. Immunoreactivity peaks between 1 week and 2 weeks postoperatively and, thereafter, remains intense for at least 24 weeks. Thus, following a lesion of the visual cortex, the somata of neurons in the LGN remain essentially normal morphologically for about 3 days before the onset of rapid atrophy and death. Moreover, most of the neural cell death that occurs in the LGN after axotomy takes place in the last half of the first postoperative week.

Long-term protection of axotomized neurons in the dorsal lateral geniculate nucleus in the rat following a single administration of basic fibroblast growth factor or ciliary neurotrophic factor.

We have studied the long-term effects of basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) on axotomy-induced cell death in the dorsal lateral geniculate nucleus (LGN) of adult rats. LGN neurons were axotomized by a visual cortex lesion in 31 adult rats. A gelatin sponge soaked in a solution of bFGF, CNTF, or saline (control) was placed on the surface of the lesion, and the animals were allowed to survive for 1-12 weeks. Compared with controls, no major improvement was noted in the mean cross-sectional area of surviving LGN neurons in rats treated with bFGF or CNTF at any survival time. However, treatment with either factor significantly increased the number of surviving neurons at each survival time. At 1 week, the survival of LGN neurons in rats treated with bFGF or CNTF was 136% and 131% greater, respectively, than in controls. At 12 weeks, the number of surviving LGN neurons in bFGF- and CNTF-treated rats exceeded that seen in controls by 114% and 58%, respectively. Thus, a single administration of bFGF or CNTF following axotomy reduced neuronal death for long periods of time, but could not prevent atrophy. A single treatment with bFGF or CNTF, therefore, may block the full execution of a cell death program, but cannot prevent its initiation. Alternatively, the transduction pathways for maintaining cell size and preventing cell death may not be identical, and bFGF and CNTF applied as described above may be effective in activating one pathway but not the other.

Dendritic field development of retinal ganglion cells in the cat following neonatal damage to visual cortex: evidence for cell class specific interactions.

A well-known feature of the mammalian retina is the inverse relation that exists in central and peripheral retina between the density of retinal ganglion cells and their dendritic field sizes. Functionally, this inverse relation is thought to represent a means by which retinal coverage is maintained, despite significant changes in ganglion cell density. While it is generally agreed that the dendritic fields of mature retinal ganglion cells reflect, in part, competitive interactions that occur during development, the issue of whether these interactions are cell class specific remains unclear. In order to examine this question, we used intracellular staining techniques and an in vitro, living retina preparation to compare the soma and dendritic field sizes of alpha and beta ganglion cells from normal retinae with those of cells located in matched areas of retinae in which the density of beta ganglion cells had been reduced selectively by neonatal removal of visual cortex areas 17, 18, and 19. Our intracellular data show that while an early, selective, reduction in beta cell density has little or no effect on the cell body and dendritic field sizes of mature alpha cells, it results in a 13% increase in the mean soma area and an 83% increase in the mean dendritic field area of surviving beta cells. This differential effect suggests that the soma and dendritic field sizes of alpha and beta ganglion cells in the mature cat retina result primarily from competitive interactions during development that are cell class specific.

Thalamic projections to the lateral suprasylvian visual area in cats with neonatal or adult visual cortex damage.

Previous transneuronal anterograde tracing studies have shown that the retino-thalamic pathway to the posteromedial lateral suprasylvian (PMLS) visual area of cortex is heavier than normal in adult cats that received neonatal damage to visual cortical areas 17, 18, and 19. In contrast, the strength of this projection does not appear to differ from that in normal animals in cats that experienced visual cortex damage as adults. In the present study, we used retrograde tracing methods to identify the thalamic cells that project to the PMLS cortex in adult cats that had received a lesion of visual cortex during infancy or adulthood. In five kittens, a unilateral visual cortex lesion was made on the day of birth, and horseradish peroxidase (HRP) was injected into the PMLS cortex of both hemispheres when the animals were 10.5 to 13 months old. For comparison, HRP was injected bilaterally into the PMLS cortex of three cats 6.5 to 13.5 months after they received a similar unilateral visual cortex lesion as adults. In cats with a neonatal lesion, retrograde labeling was found in the large neurons that survive in the otherwise degenerated layers A and A1 of the lateral geniculate nucleus (LGN) ipsilateral to the lesion. Retrograde labeling of A-layer neurons was not seen in the undamaged hemisphere of these animals or in either hemisphere of animals that had received a lesion as adults. As in normal adult cats, retrograde labeling also was present in the C layers of the LGN, the medial interlaminar nucleus, the posterior nucleus of Rioch, the lateral posterior nucleus, and the pulvinar nucleus ipsilateral to a neonatal or adult lesion. Quantitative estimates indicate that the number of labeled cells is much larger than normal in the C layers of the LGN ipsilateral to a neonatal visual cortex lesion. Thus the results indicate that the heavier than normal projection from the thalamus to PMLS cortex that exists in adult cats after neonatal visual cortex damage arises, at least in part, from surviving LGN neurons in the A and C layers of the LGN. Although several thalamic nuclei, as well as the C layers of the LGN, continue to project to PMLS cortex after an adult visual cortex lesion, these projections appear not to be affected significantly by the lesion.

Development of the projections from the dorsal lateral geniculate nucleus to the lateral suprasylvian visual area of cortex in the cat.

In the study reported in the preceding paper, we used retrograde labeling methods to show that the enhanced projection from the thalamus to the posteromedial lateral suprasylvian (PMLS) visual area of cortex that is present in adult cats following neonatal visual cortex damage arises at least partly from surviving neurons in the dorsal lateral geniculate nucleus (LGN). In the C layers of the LGN, many more cells than normal are retrogradely labeled by horseradish peroxidase (HRP) injected into PMLS cortex ipsilateral to a visual cortex lesion. In addition, retrogradely labeled cells are found in the A layers, which normally have no projection to PMLS cortex in adult cats. The purpose of the present study was to investigate the mechanisms of this enhanced projection by examining the normal development of projections from the thalamus, especially the LGN, to PMLS cortex. Injections of HRP were made into PMLS cortex on the day of birth or at 1, 2, 4, or 8 weeks of age. Retrogradely labeled neurons were present in the lateral posterior nucleus, posterior nucleus of Rioch, pulvinar, and medial interlaminar nucleus, as well as in the LGN, at all ages studied. Within the LGN of the youngest kittens, a small number of retrogradely labeled cells was present in the interlaminar zones and among the cells in the A layers that border these zones. Such labeled cells were virtually absent by 8 weeks of age, and they are not found in normal adult cats. Sparse retrograde labeling of C-layer neurons also was present in newborn kittens.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of action potentials on the development of the central visual pathway in mammals.

The development of the mammalian visual system begins prenatally at distributed sites, where cells generated at different embryonic ages are destined to interconnect and form the visual pathways, and ends postnatally with the functional tuning of neuronal receptive-field properties. It is reasonable to assume that the earliest stages in this developmental sequence are completed prior to the onset of neural activity, and also that activity may play only a minor role or even none at all in primary axon outgrowth and pathway finding (Harris, 1981; Harris and Holt, 1990). However, recent evidence indicates that subsequent events in development, such as the sorting of axons at their targets, the cellular differentiation of target cells and the formation of synaptic contacts by developing axons, are all influenced by action potentials. Action potentials in the developing retino-geniculo-cortical pathway can be eliminated by blocking the voltage-gated sodium channel with tetrodotoxin. Prenatal blockade prevents the laminar segregation of retinogeniculate axons. Postnatal blockade interrupts the formation of retinogeniculate synaptogenesis, slows the cytoarchitectonic differentiation of the lateral geniculate nucleus and produces abnormalities in the responses of lateral geniculate neurons. In the visual cortex, the development of cells and synapses is retarded and the eye-specific separation of geniculocortical axons is halted, thereby blocking the formation of ocular dominance columns. While the cellular mechanisms underlying these effects are not understood, a partial restoration of normal development can be produced by stimulating blocked axonal pathways electrically.

Synaptic connections between corticogeniculate axons and interneurons in the dorsal lateral geniculate nucleus of the cat.

Anatomical evidence is provided for direct synaptic connections by axons from visual cortex with interneurons in lamina A of the cat's dorsal lateral geniculate nucleus. Corticogeniculate axon terminals were labeled selectively with 3H-proline and identified by means of electron microscopic autoradiography. Interneurons in the lateral geniculate nucleus were stained with antibodies that had been raised against gamma aminobutyric acid (GABA). We found that corticogeniculate terminals synapsed with dendrites stained positively for GABA about three times as often as with unstained dendrites. Of the corticogeniculate terminals that contacted GABA-positive dendrites, 97% made synaptic connections with dendritic shafts. Only 3% synapsed with F profiles, the vesicle-filled dendritic appendages characteristic of lateral geniculate interneurons. These results suggest that the corticogeniculate pathway in the cat is directed primarily at interneurons and is organized synaptically to influence the integrated output of these cells, rather than the local interactions in which their dendritic specializations participate.

Development of corticogeniculate synapses in the cat.

The development of corticogeniculate synapses was studied in 16 cats ranging in age from newborn to adult. Tritiated proline was injected into areas 17 and 18 of the visual cortex in order to label corticogeniculate terminals in lamina A of the dorsal lateral geniculate nucleus. The labeled terminals were then characterized ultrastructurally using electron microscopic autoradiography. Labeled synaptic profiles were found in newborn kittens, indicating that corticogeniculate connections are present in the cat at birth. Morphologically, however, many corticogeniculate endings in newborn and 1-week-old kittens are different from those in older animals in that they do not form well-defined terminal boutons, and their synaptic vesicles are often loosely packed. In kittens 2 weeks of age and older, corticogeniculate axons end as RSD terminals exclusively; i.e., they are relatively small in size and contain round, densely packed synaptic vesicles, and occasionally an electron-dense mitochondrion (Guillery: Z. Zellforsch. 99: 1-38, '69). However, not all RSD terminals in the LGN represent input from visual cortex. Injections of 3H-proline into the mesencephalic reticular formation also label RSD terminals selectively in the lateral geniculate nucleus. At all ages corticogeniculate axons make synaptic contacts with dendrites exclusively, and they are always presynaptic. This suggests that the essential pattern of corticogeniculate synapses is formed early and is not altered during subsequent development. Quantitatively, there is no significant change in the size of corticogeniculate terminals or their synaptic vesicles in kittens 2 weeks of age (the youngest measured) and older. In contrast, the synaptic contact lengths of these terminals decreases about 28% between 2 and 12 weeks. During this same period there is approximately a twofold increase in the density of corticogeniculate terminals in the neuropil of lamina A. Since the volume of neuropil in lamina A increases almost fourfold between 2 and 12 weeks, the doubling of corticogeniculate terminal density represents about an eightfold increase in terminal number. After 12 weeks there is little change in the length, density, or number of corticogeniculate synaptic contacts, which suggests that the morphological development of the corticogeniculate pathway is essentially complete by this age.

Synaptic reorganization in the dorsal lateral geniculate nucleus following damage to visual cortex in newborn or adult cats.

We have studied the effects of making large lesions of visual cortex on the synaptic organization of the dorsal lateral geniculate nucleus (LGN) in the cat. Visual cortex was removed at birth in one group of cats and during adulthood in a second group. Following survival periods of 6 months to 2 years, the organization of synapses made by afferents from the retina in the LGN was investigated quantitatively with the electron microscope. In single thin sections we determined the percentage of retinal axon terminals that made synapses in the LGN, the average number of synapses made by each retinal axon terminal, and the identity of each postsynaptic process. These measurements were made separately for retinogeniculate connections in the A and C laminae of the LGN. For comparison, similar sets of measurements were made in adult cats that had been reared normally. When single thin sections from the A or C laminae of the LGN in normal cats are examined, about 60% of the axon terminals from the retina are seen to make at least one synaptic contact. These contacts can be with dendrites or F profiles or both. On average, each retinogeniculate terminal makes approximately 1.4 synapses in the plane of a single section and contacts dendrites three times as often as F profiles. In the A laminae of the LGN in cats that received a visual cortex lesion at birth or in adulthood, the percentage of retinal terminals that make synapses is the same as in normal cats. Similarly, the average number of synaptic contacts made by each retinogeniculate terminal is not changed by a lesion of visual cortex. In contrast, the number of contacts made with dendrites is reduced markedly, by about 29% after a lesion at birth and 53% after a lesion as an adult. However, these reductions are offset by compensatory increases in the number of contacts made with F profiles, and thus the mean number of contacts made by each retinogeniculate terminal is stabilized at a normal value. In the C laminae of the LGN, retinogeniculate terminals also reapportion their synaptic contacts. In cats with a lesion during adulthood, the redistribution of synapses is compensatory, as in the A laminae. When a lesion is made at birth, however, the number of new retinal contacts made with F profiles exceeds the number of dendritic contacts that are lost. As a result, each retinogeniculate terminal makes about 26% more synapses, in total, than normal.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of corpus callosum section on functional compensation in the posteromedial lateral suprasylvian visual area after early visual cortex damage in cats.

A visual cortex lesion made in adult cats leads to a loss of direction selectivity and a loss of response to the ipsilateral eye among cells in posteromedial lateral suprasylvian (PMLS) cortex of cats. However, a visual cortex lesion made in young cats results in normal direction selectivity and normal ocular dominance in PMLS cortex. Thus cats with an early lesion demonstrate functional compensation in PMLS cortex. The present experiment determined whether the functional compensation depends upon an intact corpus callosum. Cats received a unilateral visual cortex lesion on the day of birth (day 1) or at 8 weeks of age. When the cats were adult, the corpus callosum was sectioned and 24 hours later recordings were made in PMLS cortex ipsilateral to the visual cortex lesion. Results were compared to cats with a similar lesion and an intact corpus callosum. In cats with a lesion made on day 1, a corpus callosum section did not affect receptive-field properties or ocular dominance in PMLS cortex. Therefore, functional compensation is not dependent on input via the corpus callosum in these animals. However, in cats with a lesion made at 8 weeks. a corpus callosum section resulted in a decrease in the percentage of direction-selective cells and in the percentage of cells driven by the ipsilateral eye. Despite the decrease, the percentage of direction-selective cells still was greater than in cats with an adult unilateral visual cortex lesion. Thus, while partly dependent on callosal inputs, some functional compensation for direction selectivity remains on the basis of ipsilateral inputs.(ABSTRACT TRUNCATED AT 250 WORDS)

Genesis of interneurons in the dorsal lateral geniculate nucleus of the cat.

Most neurons in the A-laminae of the cat's dorsal lateral geniculate nucleus (LGN) are born between embryonic days 22 and 32. Whereas approximately 78% of these cells are destined to become geniculocortical relay cells, the remaining 22% of LGN neurons do not appear to establish connections with visual cortex, and therefore can be considered interneurons. In the present study we have combined the 3H-thymidine method for labeling dividing neurons with the retrograde horseradish peroxidase (HRP) method for identifying LGN relay cells in order to study specifically the genesis of interneurons in the cat's LGN. Developing LGN interneurons in 12 kittens were labeled with 3H-thymidine by injecting the radioactive label into the allantoic cavity of their pregnant mothers on different embryonic days. Approximately 8-22 weeks after birth LGN relay cells in the A-laminae were labeled retrogradely by injecting large volumes of HRP into visual cortex areas 17 and 18. LGN cells that could not be labeled retrogradely with HRP were considered to be interneurons. Our results show that interneurons are born on each of the embryonic days studied, E24-E30. This period represents approximately the middle two-thirds of the entire period of LGN neurogenesis. Although the birth rate for interneurons is not uniform, there is no indication from our data that interneurons and relay cells in the cat's LGN are born at different times during LGN neurogenesis.

Elimination of action potentials blocks the structural development of retinogeniculate synapses.

Although the influence of electrical activity on neural development has been studied extensively, experiments have only recently focused on the role of activity in the development of the mammalian central nervous system (CNS). Using tetrodotoxin (TTX) to abolish sodium-mediated action potentials, studies on the visual system show that impulse activity is essential both for the normal development of neuronal size and responsivity in the lateral geniculate nucleus (LGN), and for the eye-specific segregation of geniculo-cortical axons. There have been no anatomical studies to investigate the influence of action potentials on CNS synaptic development. We report here the first direct evidence that elimination of action potentials in the mammalian CNS blocks the growth of developing axon terminals and the formation of normal adult synaptic patterns. Our results show that when TTX is used to eliminate retinal ganglion-cell action potentials in the cat from birth to 8 weeks, the connections made by ganglion cell axons with LGN neurones, retinogeniculate synapses, remain almost identical morphologically to those in the newborn kitten.

Critical periods for functional and anatomical compensation in lateral suprasylvian visual area following removal of visual cortex in cats.

Previous experiments have found that neurons in the cat's lateral suprasylvian (LS) visual area of cortex show functional compensation following removal of visual cortical areas 17, 18, and 19 on the day of birth. Correspondingly, an enhanced retino-thalamic pathway to LS cortex develops in these cats. The present experiments investigated the critical periods for these changes. Unilateral lesions of areas 17, 18, and 19 were made in cats ranging in age from 1 day postnatal to 26 wk. When the cats were adult, single-cell recordings were made from LS cortex ipsilateral to the lesion. In addition, transneuronal autoradiographic methods were used to trace the retino-thalamic projections to LS cortex in many of the same animals. Following lesions in 18- and 26-wk-old cats, there is a marked reduction in direction-selective LS cortex cells and an increase in cells that respond best to stationary flashing stimuli. These results are similar to those following visual cortex lesions in adult cats. In contrast, the percentages of cells with these properties are normal following lesions made from 1 day to 12 wk of age. Thus the critical period for development of direction selectivity and greater responses to moving than to stationary flashing stimuli in LS cortex following a visual cortex lesion ends between 12 and 18 wk of age. Following lesions in 26-wk-old cats, there is a decrease in the percentage of cells that respond to the ipsilateral eye, which is similar to results following visual cortex lesions in adult cats. However, ocular dominance is normal following lesions made from 1 day to 18 wk of age. Thus the critical period for development of responses to the ipsilateral eye following a lesion ends between 18 and 26 wk of age. Following visual cortex lesions in 2-, 4-, or 8-wk-old cats, about 30% of the LS cortex cells display orientation selectivity to elongated slits of light. In contrast, few or no cells display this property in normal adult cats, cats with lesions made on the day of birth, or cats with lesions made at 12 wk of age or later. Thus an anomalous property develops for many LS cells, and the critical period for this property begins later (between 1 day and 2 wk) and ends earlier (between 8 and 12 wk) than those for other properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Response properties of striate cortex neurons in cats raised with divergent or convergent strabismus.

Recordings were made from striate cortex in five groups of cats that had been raised with strabismus produced by sectioning the extraocular muscles. These groups included animals reared with exotropia, unilateral or bilateral esotropia, and esotropia combined with lid suture of the unoperated eye. In addition, a group of esotropes was studied in which the unoperated eye was removed a few hours prior to recording. For comparison, five normal adult cats were also studied. In each of the above groups, cells were sampled in the representations of the central and peripheral visual fields in area 17 ipsilateral and contralateral to the deviated eye. We mapped the receptive field of each responsive cell, determined its ocularity, and tested it for selectivity. Confirming previous work, we found a marked loss of cortical binocularity in cats raised with strabismus. On average only 7% of the neurons that we recorded could be driven by both eyes. This percentage was relatively constant at all cortical locations that were studied and was not influenced by whether cats had been reared with exotropia, unilateral esotropia, or bilateral esotropia. The percentage of selective cells driven by the deviated eye in exotropes or esotropes did not appear to be different from normal at most cortical locations (but see 5, below). In addition, we did not observe any bias in the axial preference of selective cells in strabismic cats when compared with normal adult cats. In both exotropes and esotropes the deviated eye drove fewer cells when compared with the proportion that are driven by one eye in normal cats. In exotropes this deficit did not vary at different cortical representations of the visual field. In esotropes, however, this deficit was graded, being least in the representation of the peripheral visual field in area 17 contralateral to the deviated eye, intermediate in the representations of the central visual field in the contralateral and ipsilateral hemispheres, and greatest in the representation of the peripheral visual field in ipsilateral area 17. Furthermore, only when recording from the peripheral field representation in the ipsilateral hemisphere did we encounter significant numbers of cells driven by the deviated eye that lacked normal selectivity. Since it is possible that deprivation of the converged eye during development might account for the deficits noted above, we attempted to evaluate this factor using several independent lines of evidence. First, we could find no correlation between the angle of esotropia and the ability of the deviated eye to drive ipsilateral cortical cells representing the peripheral visual field.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of strabismus on responsivity, spatial resolution, and contrast sensitivity of cat lateral geniculate neurons.

Rearing cats with esotropia is known to cause a number of deficits in visual behavior tested through the deviated eye. These include a loss of orienting response to stimuli presented in the nasal visual field of the deviated eye, a reduction in visual acuity, and a general reduction in contrast sensitivity at all spatial frequencies. To assess the involvement of the lateral geniculate nucleus (LGN) in these deficits, we measured the following: 1) the visual responsiveness of lamina A1 cells with peripheral (more than 10 degrees from area centralis) receptive fields in three esotropic and three normal cats and 2) the spatial resolution and contrast sensitivity of lamina A X-cells with central (within 5 degrees of the area centralis) receptive fields in six esotropic and six normal cats. For comparison, we also measured LGN X-cell spatial resolutions in four exotropic cats and in two cats raised with an esotropia in one eye and the lids of the other eye sutured shut (MD-estropes). Recordings from the lateral portion of lamina A1 in esotropic cats yielded similar numbers of visually responsive cells with far nasal receptive fields as were seen in normal animals. Peak and mean response rates to a flashing spot also were normal. In addition, no differences were found between esotropes and normals in the percentages of X- and Y-cells encountered. These results suggest that the loss of orienting response to stimuli presented in the nasal field (12, 20) is not due to a loss of neural responses in the LGN of esotropic cats. In addition, they suggest that decreases in cell size in lamina A1 of esotropic cats (13, 36; R. E. Kalil, unpublished observations) are not accompanied by marked functional abnormalities of the cells and that cortical abnormalities ipsilateral to the deviated eye (22) are likely to have their origin within striate cortex itself. Recordings from lamina A cells with receptive fields near area centralis revealed that the average X-cell spatial resolution in esotropes (2.1 cycles/deg) was significantly lower than that in normal cats (3.1 cycles/deg). This reduction was seen in all esotropic cats tested and was due both to an increase in the proportion of X-cells with very low spatial resolution and to a loss of X-cells responding to high spatial frequencies (greater than 3.25 cycles/deg). The average spatial resolution of X-cells driven by the deviated eye in MD-esotropes fell midway between those of esotropes and normals. In exotropes, mean X-cell spatial resolution was normal.(ABSTRACT TRUNCATED AT 400 WORDS)

The percentage of interneurons in the dorsal lateral geniculate nucleus of the cat and observations on several variables that affect the sensitivity of horseradish peroxidase as a retrograde marker.

Ten cats ranging in age from 4 weeks postnatal to adult received large bilateral injections of horseradish peroxidase (HRP) into cortical areas 17 and 18. In one cat additional unilateral injections of HRP were made into the lateral suprasylvian visual areas (PMLS). The purpose of these injections was to label relay cells in lamina A of the dorsal lateral geniculate nucleus (LGN), in order to distinguish them from neurons that could not be labeled retrogradely. Several factors thought to influence the effectiveness of HRP as a retrograde marker were varied in an effort to label as many relay cells as possible. These factors included the (1) rate and duration of HRP injections; (2) volume and concentration of HRP injected; (3) addition of L-alpha-lysophosphatidylcholine or dimethyl sulfoxide to the injected HRP; and (4) aldehyde and buffers used for fixation. In all experiments DAB (3,3'-diaminobenzidine tetrahydrochloride) was used as the chromogen, either alone or with the addition of cobalt chloride, nickel, and cobalt salts, or cobalt-glucose oxidase. In 1-micrometer plastic sections, the influence of each of the above factors and DAB methods was determined by measuring the percentage of unlabeled neurons and the cytoplasmic HRP grain density of cells that were labeled. Our results show that approximately 22% of the neurons in lamina A of the LGN remain unlabeled following injections of HRP into areas 17 and 18 alone or combined with injections into PMLS. The percentage of unlabeled cells is similar at each of the ages that we studied and is not affected significantly by any of the factors that were varied or DAB methods that were used. Cross-sectional area measurements show that unlabeled cells tend to be among the smallest neurons in lamina A. Regardless of age, the mean size of labeled neurons was about twice that of unlabeled cells. However, we found only a weak correlation between the size of a labeled cell and the cytoplasmic density of HRP grains. Thus it is unlikely that small cell body size alone can account for the unlabeled cells in lamina A, since small neurons can be as effective in transporting HRP retrogradely as large neurons. We therefore conclude that there is a distinct population of small neurons in lamina A of the LGN that do not project to cortex. Although we cannot rule out the possibility that these cells project subcortically, we believe that it is reasonable to regard them as interneurons.

Visual-evoked responses from strabismic cats. A comparison of esotropes with exotropes.

We examined cortical responses evoked by 8-Hz, phase-shifted sine wave gratings at a range of contrasts and spatial frequencies in normal cats and in cats raised with artificial esotropia or exotropia. There were no significant differences between the amplitudes of the responses evoked through the two eyes of the normal cats, but for some esotropes and exotropes the responses evoked through the unoperated eye were larger than those evoked through the operated eye. Interocular response differences were comparable in all affected cats and were most pronounced at high contrasts. These results indicate that rearing with artificial strabismus can produce amblyopia in both esotropes and exotropes, and that the amblyopia is similar in the two cases.

Thalamic projections to visual areas of the middle suprasylvian sulcus in the cat.

The thalamic afferents to two areas of the lateral suprasylvian visual cortex in the cat were studied by using retrograde transport of horseradish peroxidase (HRP). Injections were localized retinotopically with electrophysiological recording. The posteromedial lateral suprasylvian area (PMLS) of Palmer et al. ('78) receives afferents from the pulvinar (P), the posterior nucleus of Rioch (PN), the C-laminae of the lateral geniculate nucleus (LGNd) and the centrolateral (CL), lateral posterior (LP), medial interlaminar (MIN) nuclei. The anteromedial lateral suprasylvian area (AMLS) receives afferents from CL, P, LP, PN, MIN, and probably from the posterior nuclear group (PO), and the lateral dorsal (LD) and ventral anterior (VA) nuclei. The LP-pulvinar complex has been divided into four zones on the basis of connectivity: geniculate wing, pulvinar, the lateral division of LP, and the interjacent division of LP (Updyke, '77; Graybiel and Berson, '80; Guillery et al., '80). The locations of labeled cells in the present experiments suggest that both AMLS and PMLS receive afferents from each of the four zones, although differences exist in the strength of the projections. While AMLS and PMLS receive afferents from many of the same nuclei (CL, P, LP, PN, and MIN), differences in their afferents also were noted. These differences are of three types. The first is that some nuclei project to only one of the cortical areas. PMLS alone receives input from the C-laminae of the LGNd while AMLS alone receives probable input from PO, LD, and VA. The second difference is in the strength of the projection from some nuclei. AMLS receives a stronger projection from CL and P than does PMLS. The third difference concerns the pattern of distribution of neurons that project to each cortical area. Labeled cells in LP are dispersed after an AMLS injection, but are found in clusters or bands after a PMLS injection. Thus our results indicate that the thalamic afferents to AMLS and PMLS are in general similar: however, differences in input to AMLS and PMLS suggest that inputs to PMLS are predominantly visual while AMLS receives a broader spectrum of afferent information.