'Top-down' influences of ipsilateral or contralateral postero-temporal visual cortices on the extra-classical receptive fields of neurons in cat's striate cortex.

In anesthetized and immobilized domestic cats, we have studied the effects of brief reversible inactivation (by cooling to 10 degrees C) of the ipsilateral or contralateral postero-temporal visual (PTV) cortices on: 1) the magnitude of spike-responses of neurons in striate cortex (cytoarchitectonic area 17, area V1) to optimized sine-wave modulated contrast-luminosity gratings confined to the classical receptive fields (CRFs) and 2) the relative strengths of modulation of CRF-induced spike-responses by gratings extending into the extra-classical receptive field (ECRF). Consistent with our previous reports (Bardy et al., 2006; Huang et al., 2007), inactivation of ipsilateral PTV cortex (presumed homologue of primate infero-temporal cortex) resulted in significant reversible changes (almost all substantial reductions) in the magnitude of spike-responses to CRF-confined stimuli in about half of the V1 neurones. Similarly, in half of the present sample, inactivation of ipsilateral PTV cortex resulted in significant reversible changes (in over 70% of cases, reduction) in the relative strength of ECRF modulation of the CRF-induced spike-responses. By contrast, despite the fact that receptive fields of all V1 cells tested were located within 5 degrees of representation of the zero vertical meridian, inactivation of contralateral PTV cortex only rarely resulted in significant (yet invariably small) changes in the magnitude of spike-responses to CRF-confined stimuli or significant (again invariably small) changes in the relative strength of ECRF modulation of spike-responses. Thus, the ipsilateral, but not contralateral, 'higher-order' visual cortical areas make significant contribution not only to the magnitude of CRF-induced spike-responses but also to the relative strengths of ECRF-induced modulation of the spike-responses of V1 neurons. Therefore, the feedback signals originating from the ipsilateral higher-order cortical areas appear to make an important contribution to contextual modulation of responses of neurons in the primary visual cortices.

Retinal ganglion cell classes in the Old World monkey: morphology and central projections.

Labeled ganglion cells were studied in whole-mount retinas of Old World monkeys after electrophoretic injections of horseradish peroxidase into physiologically characterized sites. A number of different morphological classes have been identified, each of which has a distinctive pattern of central projection. Since different functional classes of primate retinal ganglion cells also have distinctive patterns of central projection, correspondences between functional and morphological cell types have been inferred. There prove to be parallels between morphological types of cat monkey ganglion cells.

Feedback signals from cat's area 21a enhance orientation selectivity of area 17 neurons.

We have studied the contribution of feedback signals originating from one of the "form-processing" extrastriate cortical areas, area 21a (A21a), to orientation selectivity of single neurons in the ipsilateral area 17 (A17). Consistent with previous findings, reversible inactivation (cooling to 5-10 degrees C) of area 21a resulted in a substantial reduction in the magnitude of the maximum response (R (max)) of A17 cells accompanied by some changes in the half-width at half-height of the R (max) (HWHH). By fitting model functions to the neurons' response profiles we found that in the vast majority of orientation-tuned A17 cells tested (30/39, 77%), inactivation of A21a resulted in a "flattening" of their orientation-tuning curves. It is characterised by a substantial reduction in the R (max) associated with either a broadening of the orientation-tuning curves (17 cells) or a relatively small reduction (12 cells) or no change (1 cell) in the HWHH. When the "flattening" effect was quantified using a simple ratio index or R/W, defined as R (max)/HWHH, we found that R/W was significantly reduced during inactivation of A21a. The change in R/W is strongly correlated with the change in the maximum slope of the orientation-tuning curves. Furthermore, analysis of response variability indicates that "signal-to-noise" ratio of the responses of A17 neurons decreases during inactivation of A21a. Our results suggest that the predominately excitatory feedback signals originating from A21a play a role in enhancing orientation selectivity of A17 neurons and hence are likely to improve overall orientation discriminability.

Ontogeny of the primate fovea: a central issue in retinal development.

The formation of the primate fovea has fascinated a substantial number of histologists, pathologists, ophthalmologists and physiologists for more than a century. In this article, using data from the literature as well as our own observations, we identify events which we believe are crucial in this process and present a developmental neurobiologist's view of the formation of the primate fovea. The fovea is a region of the retina specialized for diurnal, high acuity functions which require a high spatial density of cone photoreceptors as well as a large number of inner retinal cells in order to establish the distinct retinofugal pathways (ganglion cell axons) receiving from individual cones in the foveal cone mosaic. A unique feature of the fovea is the displacement of cells connected to the foveal cones onto the rim of the fovea. It is generally believed that this displacement counteracts the problems caused by the scattering of the incoming light by cells and blood vessels of the inner retina. We believe that one of the crucial events in the formation of the primate fovea is the early centripetal migration of photoreceptors towards the central area (centripetal displacement). This process, initiated early in development, continues throughout intrauterine life until some months or years postnatal. We propose that the displacement of cells from the inner layers is related to the earlier developmental accumulation of photoreceptors and inner retinal cells centrally. This, we propose, leads to metabolic "starvation" of the inner retina, resulting from the complete absence of retinal vessels from the vicinity of the incipient fovea. It is suggested that these factors in turn trigger centrifugal displacement of inner retinal cells towards the encroaching perifoveal capillary network and lead to the formation of the foveal depression.

Bihemispheric Collateralization of the Cortical and Subcortical Afferents to the Rat's Visual Cortex.

A fluorescent dye (usually fast blue or rhodamine tagged latex microspheres) was injected into cortical area 17 (or area 17 and the lateral part of area 18b) of adult and juvenile (15 - 22 day old) Sprague-Dawley albino rats. Another fluorescent dye (usually diamidino yellow) was injected into cortical areas 17, 18a and 18b of the opposite hemisphere. The injections involved only the cortical grey matter. After postinjection survival of 2 - 14 days the distribution of retrogradely labelled mesencephalic and prosencephalic cells was analysed. Both small and large injections labelled retrogradely a substantial number of cells in specific and nonspecific dorsal thalamic nuclei (lateral geniculate, lateral posterior, ventromedial, several intralaminar nuclei and nucleus Reuniens) as well as a small number of cells in the preoptic area of the hypothalamus and the mesencephalic ventral tagmental area (VTA). While labelled thalamic cells contained only the dye injected into the ipsilateral cortex, a small proportion of hypothalamic and VTA cells was labelled with the dye injected into the contralateral cortex. Virtually none of the cells in these areas were double labelled with both dyes. Both small and large injections labelled cells in the ipsilateral telencephalic magnocellular nuclei of the basal forebrain and the caudal claustrum. A substantial minority of labelled cells in these structures was labelled by the dye injected into the contralateral cortex. Furthermore, a small proportion (about 1%) of claustral cells projecting to the ipsilateral cortex were double labelled with both dyes. In several cortical areas ipsilateral to the injected area 17, associational neurons were intermingled with commissural neurons projecting to the contralateral visual cortex. A substantial proportion of associational neurons projecting to ipsilateral area 17 also projected to the contralateral visual cortex (associational-commissural neurons). Thus, in visual area 18a, the associational-commissural neurons were located in all laminae, with the exception of lamina 1 and the bottom of lamina 6, and constituted about 30% of the neurons projecting to ipsilateral area 17. In paralimbic association area 35/13, associational-commissural neurons were located in lamina 5 and constituted about 20% of neurons projecting to ipsilateral area 17. In the limbic area 29d, the associational-commissural neurons were located in laminae 4, 5 and the upper part of lamina 6 and constituted about 10% of the associational-commissural neurons projecting to ipsilateral area 17. In oculomotor area 8, double-labelled neurons were located in lamina 5 and constituted about 10% of the neurons projecting to ipsilateral area 17. Thus, it appears that the axons of mesencephalic and diencephalic neurons projecting to the visual cortex do not send collaterals into both hemispheres. The bihemispheric projection to the rat's visual cortex originates almost exclusively in the retinotopically organized cortical area 18a and in integrative cortical areas 35/13, 29d and 8.

Bihemispheric Axonal Bifurcation of the Afferents to the Visual Cortical Areas during Postnatal Development in the Rat.

Numerous cortical neurons in the juvenile and adult rat project to visual areas of both hemispheres whereas the vast majority of subcortical structures projecting to the visual cortex send strictly ipsilateral projections (Dreher et al., 1990). In the present study, the authors have sought to determine whether this pattern of axonal bifurcation in the connectivity of the visual areas undergoes a change during postnatal development. Two retrograde fluorescent dyes were used, fast blue (FB) and diamidino yellow (DY). Large multiple injections of one of the dyes were placed in all visual areas of one hemisphere and a small injection of the other dye was placed in area 17 of the opposite hemisphere. Labelled neurons were observed in subcortical and cortical structures on the side of the small injection. The experiments were performed on ten neonatal albino rat pups aged between 3 and 12 postnatal days (p.n.d.) at the time of injection and the results were compared with those obtained in the juvenile and adult animals, as reported in the preceding paper. In the thalamus of newborn animals, neurons belonging to nuclei located away from the midline send strictly ipsilateral cortical projections. However, in the midline nuclei of the intralaminar thalamic complex, a small region of overlap was observed between neurons projecting ipsilaterally and neurons projecting contralaterally in animals aged less than 9 postnatal days. In addition, in these neonatal animals a small number of bilaterally projecting neurons was detected in this region of overlap. In all other subcortical structures examined (ventral tegmental area, diagonal band of Broca, claustrum), the laterality of the projection was the same in the newborn and the adult animals. In particular, in the claustrum of neonatal animals, as in adult animals, there was a large contingent of contralaterally projecting neurons and only a very small number of bilaterally projecting neurons. The results in the cortex contrast with those observed in subcortical structures. Whereas ipsilaterally projecting neurons were distributed in a broadly similar way in newborn and adult animals, the laminar and areal distribution of contralaterally projecting neurons in newborn animals clearly differed from those observed in the adult animals. Furthermore, double labelled neurons were more numerous in animals aged less than 12 days than in adults. The proportions of such bilaterally projecting neurons were computed with respect to the numbers of neurons sending ipsilateral projections to area 17. These proportions are constant at all ages in the claustrum and cortical area 8. In areas 18a, 29 and 35 on the other hand, the proportions of bilaterally projecting neurons increase after 5 days and reach a peak in the period extending from 9 to 11 days of age when more than half of the neurons projecting ipsilaterally also send an axonal branch to the contralateral cortex. In cortical areas 29 and 35, this peak is followed by a sudden drop to the adult level at 12 postnatal days, whereas the return to the adult level is gradual in area 18a. These results demonstrate that, in subcortical structures and in cortical area 8, the laterality of the afferent connections to the visual cortex does not change during postnatal development. By contrast, cortical areas 18a, 29 and 35 go through a stage when numerous cells send bifurcating connections to both hemispheres. The timing of the decrease in proportions of bilaterally projecting neurons in these areas suggests that numerous neurons retract their callosal axonal branch when the adult pattern of callosal connectivity is established at 9 - 11 days of age.

Spatiotemporal patterns of ontogenetic expression of parvalbumin in the superior colliculi of rats and rabbits.

We have examined the development of parvalbumin immunoreactivity in the superior colliculi (SC) of the perinatal and mature rats and rabbits. In mature animals, parvalbumin-expressing cells (PECs) and neuropil in the retinorecipient layers were distributed in a continuous single band extending throughout the entire extent of the colliculus, whereas those in the intermediate layers formed distinct, radially oriented patches. Parvalbumin was expressed for the first time on postconceptional day 34 (PCD 34, postnatal day 12) and PCD 42 (postnatal day 11) in the SC of rat and rabbit, respectively. During ensuing development, both the thickness of the parvalbumin-expressing band in the retinorecipient layers and the numbers of PECs in this band gradually increased, reaching adultlike values by PCD 44 and PCD 50 in the rat and rabbit, respectively. In the rat, monocular eye enucleations on PCD 23 resulted in approximately 55% reduction in the number of PECs in the retinorecipient layers of the contralateral colliculi examined on PCD 44 or PCD 50. Unilateral ablations of the entire visual cortex on PCD 23 (before the first corticotectal fibers from visual cortices reach the SC) or on PCD 28 (when about half of the corticotectal fibers have reached colliculus) resulted in, respectively, approximately 55% and approximately 25% relative reduction in the number of PECs in the retinorecipient layers of the ipsilateral colliculi examined on PCD 44 or PCD 50. We conclude that the ontogenetic expression of parvalbumin in most of PECs in the retinorecipient collicular layers is induced by the activity of the contralateral retinotectal and/or the activity of the ipsilateral corticotectal afferents.

Vitread proliferation of filamentous processes in avian Müller cells and its putative functional correlates.

In order to examine to what extent the neuronal and metabolic activities of avascular vertebrate retinae are reflected in the morphology of their Müller cells we have studied (by using several monoclonal antibodies) the morphology of Müller cells in two species of diurnal birds (chicken, Gallus domesticus, and pigeon, Columba livia) and one species of nocturnal saltwater crocodiles (Crocodylus porosi). In all three species, the outer nuclear layer is relatively thin and the Müller cell trunks divide into rootlets that wrap around the photoreceptors. In both diurnal birds studied, the trunks of Müller cells in the inner plexiform layers invariably divide into numerous fine filamentous processes that terminate in small expansions covering most of the vitreal surface of the retina. Furthermore, the networks of filamentous processes of birds' Müller cells exhibit conspicuous horizontal lamination in the inner plexiform layer. In contrast, the filamentous processes arising from the individual Müller cell trunks of the crocodile, if present, are much less numerous and less widely spread than those of diurnal birds. It is proposed that the splitting of the Müller cell trunks into numerous filamentous processes terminating in small vitreal expansions represents a morphological adaptation for: 1) effective spatial buffering of K+ ions in thick and presumably metabolically highly active, yet avascular, avian retinae, and 2) effective absorption and distribution of nutrients leaking from the vitreally located supplemental nutritive organ, the pecten.

Retinal W-cell projections to the medial interlaminar nucleus in the cat: implications for ganglion cell classification.

The perikaryal sizes and retinal distribution of ganglion cells labeled after small iontophoretic injections of horseradish peroxidase (HRP) into the medial interlaminar nucleus (MIN) were studied. Injections were also made into the LGNv and the C-laminae of the dorsal lateral geniculate nucleus (LGNd) for comparison. The results are consistent with suggestions that the MIN contains three approximately vertically oriented laminae which, from medial to lateral, receive their input from, respectively, contralateral nasal, ipsilateral temporal, and contralateral temporal retina. Each MIN lamina receives afferents from two distinct groups of retinal ganglion cells (1) cells with large somas (over 25 micron), coarse primary dendrites, large dendritic trees (500-900 micron in diameter), and coarse axons; (2) cells with medium-sized somas (14-20 micron), medium-caliber primary dendrites, large dendritic trees (350-700 micron), and fine axons. The large cells are clearly Y-cells or alpha cells, and they provide approximately 50% of the retinal input to all layers of the MIN. The medium-sized cells, which provide the remaining 50% of the retinal output in the MIN, are, we argue, W-cells, since they do not differ in soma size, dendritic morphology, axon caliber, or receptive field properties from medium-sized W-cells which project to other thalamic or midbrain structures. These results suggest two phylogenetic trends within the W-cell group: (1) the differentiation of thalamic and midbrain components; and (2) the further differentiation of ipsilateral and contralateral projections within the midbrain component. This latter division corresponds to the distinction between W1 and W2 cells described previously (Rowe and Stone, '77, '80).

Properties of neurons in cat's dorsal lateral geniculate nucleus: a comparison between medial interlaminar and laminated parts of the nucleus.

We studied the receptive field properties of 460 cells in the cat's dorsal lateral geniculate nucleus (LGNd), 108 cells were located in the medial interlaminar nucleus (MIN) and 352 in the laminated part of the LGNd. In both the MIN and laminated parts of the LGNd, relay cells belonging to all three functional classes (W, X and Y) have been identified. Of cells in the laminated LGNd, about 32.5% were Y cells, about 54.5% were X cells and about 8.5% were W cells. By contrast, in the MIN, about 84% were Y cells, only about 4.5% being X cells and about 7.5%, W cells. In the laminated LGNd, Y cells represented 25% of cells with receptive fields near the area centralis (0-3 degrees eccentricity group) and about 42% in the group of cells with the most peripherally located receptive fields (20-40 degrees eccentricity group). A similar but much weaker trend was observed in the MIN. In the laminated LGNd but not in the MIN the receptive field center sizes increased with increasing eccentricity of receptive field position. At any eccentricity, receptive field centers of MIN Y cells tended to be larger than those of Y cells in the laminated LGNd. Response latency ranges to orthodromic and antidromic stimulation were the same for cells located in the laminated LGNd and those in the MIN. However, the mean response latency to stimulation of the optic chiasm was significantly shorter for Y cells in MIN than for Y cells in the laminated LGNd. Our results suggest that the most numerous cells observed histologically in the MIN, class 1 cells of Guillery ('66) are morphological equivalents of Y cells.

Projections from striate and extrastriate visual cortices of the cat to the reticular thalamic nucleus.

We have studied the pattern of connectivity of the visual cortical areas 17, 18, 19, 20a, 21a, posteromedial lateral (PMLS), and the posterolateral lateral (PLLS) suprasylvian areas with the reticular thalamic nucleus (RTN) of the cat ventral thalamus. Three cortical areas per hemisphere were injected iontophoretically with either 4% wheat germ agglutinin-horseradish peroxidase, 4% dextran-fluororuby, or 4% dextran-biotin. The visual field representations of the injection sites were determined by reference to previously published visuotopic maps of the cortex. The locations of labelled fibres, presumed terminals and cell bodies were determined with the aid of a camera lucida attachment and computer aided stereometry. In the ventral thalamus, the primary visual cortices (areas 17 and 18) project in a topographic manner to both the perigeniculate nucleus (PGN) and the RTN. By contrast, the "higher" visual cortical areas (areas 19, 21a, 20a, PMLS, and PLLS) project only to the RTN. Our experiments demonstrate the existence of a single, albeit coarse, visuotopic map within the RTN but do not support the notion of separate subregions within the RTN that can be related specifically to a particular visual cortical area. The putative single visuotopic map in the RTN appears to be organised in such a way that the vertical meridians are represented along the rostrocaudal axis of the RTN, whereas the horizontal meridians are mapped within the dorsoventral axis of the nucleus. The upper visual field is represented within regions of the RTN adjacent to the caudal part of the dorsal lateral geniculate nucleus (LGNd), whereas the lower visual field is represented in the parts of the RTN rostral to the LGNd. The map also shows a ventrodorsal shift along the rostrocaudal axis of the RTN such that in the rostral RTN the representation of vertical meridian is placed more ventrally than that in the caudal part of the nucleus.

Central projections of cat retinal ganglion cells.

The central projections of different groups of cat retinal ganglion cells were studied following small iontophoretic injections of horseradish peroxidase (HRP) into physiologically characterized sites. Analysis was restricted to labeled cells in the upper periphery of the nasal retina, contralateral to the injection site. Injections were made to the A lamina and C lamina of the dorsal lateral geniculate nucleus (LGNd-A,C), the geniculate wing (LGNd-W), the ventral lateral geniculate nucleus (LGNv), the pretectum (PT), and the superior colliculus (SC). The dendritic fields of alpha, beta, and epsilon cells were well labeled by the procedures we employed. A group, termed "g1," had somal sizes within the range of the smaller beta and epsilon cells, but dendritic morphologies distinct from either class. The g1 group may consist of a number of types, but our material provided no basis for further distinguishing them. Many cells were observed that had smaller somas; all had thin axons, and few had dendritic fields that labeled to any significant extent. We were not able to further distinguish these cells, and refer to this group, which may include a number of types, as "g2" cells. From the peripheral nasal retina, alpha cells project to LGNd-A, LGNd-C, PT, and SC. Beta cells project to LGNd-A, LGNd-C, and PT. Epsilon and g1 cells project to the LGNd-C, LGNd-W, LGNv, PT, and SC. We determined the total spatial density of cells in the region of the retina analyzed, using a Nissl-stained preparation. We then estimated the relative fraction of cells in each of the above groupings by injecting HRP throughout a cross section of the optic tract. Multiplying this relative fraction by the total spatial density gave an estimate of the spatial density of each of these groupings. From the spatial density of cells labeled from the injection site, we were able to estimate the fraction of cells of each retinal grouping that project to each of the zones investigated. By these calculations, almost all alpha cells from the upper nasal retina project to LGNd-A and LGNd-C; most project to SC, and about a third to PT. Beta cells, by contrast, project almost exclusively to LGNd-A, with about 10% going to LGNd-C, and about 1% to the PT. The great majority of epsilon cells, if not all, project to LGNd-W, and up to half of this population also project to the other zones noted above.(ABSTRACT TRUNCATED AT 400 WORDS)

Spatiotemporal pattern of ontogenetic expression of calbindin-28/kD in the retinorecipient layers of rat superior colliculus.

Using an antibody against calbindin-28kD, we have studied the spatial pattern of expression of this protein in the superior colliculi (SC) of four strains of mature laboratory rats. In all four strains, calbindin-expressing cells (CECs) formed horizontally oriented tiers in the retinorecipient and intermediate gray layers but were diffusely distributed throughout the deep layers. Ontogenetically, calbindin-28kD was expressed for the first time in the retinorecipient layers at postconceptional day 20 (PCD 20), by cells located in the rostrolateral region where the first born retinal ganglion cells (RGCs) are represented. Although on the day of birth (PCD 22/23), the CECs were distributed more widely, they were still absent in the most medial part of the SC, that is, the region where the latest born RGCs are represented. The spatial distribution of CECs became adultlike only by PCD 29, that is, at the end of the period of the naturally occurring death of the RGCs. Monocular eye enucleations on PCD 23 prevented the expression of calbindin in the medial fifth of the retinorecipient layers of the contralateral SC, while the unilateral removal of the visual cortices had no discernable effect on the numbers and distribution of the CECs in either SC. Thus, the spatiotemporal pattern of ontogenetic expression of calbindin-28kD in the retinorecipient layers of SC reflects the spatiotemporal pattern of generation of the RGCs, and the retinal input appears to induce neuronal expression of calbindin-28kD in these layers.

Role of target tissue in regulating the development of retinal ganglion cells in the albino rat: effects of kainate lesions in the superior colliculus.

Kainic acid or ibotenic acid was injected unilaterally into the major target regions of the axons of retinal ganglion cells--the superior colliculus (SC) or dorsal lateral geniculate nucleus (DLG)--of rat pups ranging in age from postnatal day 0 to postnatal day 10 (P0 - P10). While the collicular or geniculate neurons within the injection site died within 48 hours of the injection, damage to axons and terminals of extrinsic origin within the injected region was not apparent. The neuronal degeneration induced by the neurotoxins, observed at both the light and electron microscopic levels, resembled the neuronal degeneration that occurs in the colliculus during normal development. Macrophages were identified in the regions containing degenerating cells. Two to three weeks after the injections of neurotoxin, massive injections of the enzyme, horseradish peroxidase (HRP), were made into the retinorecipient nuclei. After about 24-hour survival time the numbers of retinal ganglion cells were estimated by counting the number of neurons containing HRP reaction products in sample areas distributed in a regular rectangular array across the entire retinal surface. In the animals in which the neurotoxin was injected into the SC during the first 4 postnatal days, there was a substantial reduction (on average 41.5%; the range: 27.5-65.5%) in the normal number (mean value of 113,000--Potts et al.: Dev. Brain Res. 3:481-486, '82) of retinal ganglion cells surviving the period of "naturally occurring ganglion cell death" in the retinae contralateral to the injected SC. By contrast, injections of neurotoxins into the DLG and/or the optic tract of newborn rats did not result in a significant reduction in the numbers of retinal ganglion cells surviving the period of naturally occurring ganglion cell death. The period of sensitivity of retinal ganglion cells to the injection of neurotoxin into the colliculi extends from birth to about the end of the first postnatal week; the greatest sensitivity seems to be restricted to the first 3-4 postnatal days. In the retinae in which the total number (and density) of ganglion cells was substantially reduced by the selective destruction of their target cells, the centro-peripheral difference in the somal diameters of the ganglion cells (apparent in normal animals) was abolished, both amongst the whole population of ganglion cells and amongst the ganglion cells with the largest somata, relatively thick axons, and large-gauge primary dendrites (Class I cells). The number and distribution of the Class I cells in the depleted retinae were, however, unaltered.(ABSTRACT TRUNCATED AT 400 WORDS)

Lymphatic metastasis; lymphangiochemotherapy of mammary cancer: ascitic form of rat mammary adenocarcinoma 13762.

When 5 million cells of the ascitic form of the RMT 13762 are injected into syngeneic F344 rat footpads there is consistent metastasis to the popliteal node more rapidly than when the solid form is used. A greater number of tumor cells escapes from the footpad to the draining node via the afferent lymph than with the solid tumor. Local intralymphatic injection of 5FU produces cure or retardation of nodal metastasis in a significant number of animals (p less than 0.002).

Extent of bilateral collateralization among pontomesencephalic tegmental afferents to dorsal lateral geniculate nuclei of pigmented and albino rats.

In adult pigmented and albino rats, small amounts of different fluorescent dyes (Fast Blue and Fluoro-Gold) were pressure-injected into the dorsal lateral geniculate nuclei, each nucleus (right or left) being injected with one dye only. After postinjection survival of three days, the distribution of neurons retrogradely labelled by each dye was analysed. Consistent with previous studies, in each strain each dye labelled a large number of neurons in the several ipsilateral visuotopically or retinotopically organized structures--visual cortices, retino-recipient layers of the superior colliculi and the pretectal nuclei. A substantial number of retrogradely labelled neurons was also found in the contralateral parabigeminal nucleus. A few retrogradely labelled neurons were found in the ipsilateral and (to a lesser extent) contralateral dorsolateral divisions of the periaqueductal gray matter, as well as in the ipsilateral parabigeminal nucleus and the caudal part of the lateral hypothalamus. However, in all the above structures there was a paucity of cells retrogradely labelled with both dyes (double-labelled cells). By contrast, in each strain, several "modulatory" nuclei (containing cholinergic and aminergic cells) of the pontomesencephalic tegmentum--dorsal raphe, pedunculopontine tegmental nucleus, parabrachial nucleus, laterodorsal tegmental nucleus and locus coeruleus--contained significant numbers of cells projecting to both ipsilateral and contralateral dorsal lateral geniculate nuclei. In each nucleus, ipsilaterally and contralaterally projecting cells constituted, respectively, about 65-70% and about 30-35% of retrogradely labelled cells. About 25% of the contralaterally projecting cells (i.e. about 5-10% of all retrogradely labelled tegmental neurons) were double-labelled with both dyes. Double-labelled cells were intermingled with single-labelled cells projecting ipsilaterally or contralaterally. The proportions of the ipsilaterally, contralaterally and bilaterally projecting neurons in the modulatory components of the pontomesencephalic tegmentum were virtually identical in pigmented and albino strains. It appears that in both strains the visuotopically organized structures convey to the dorsal lateral geniculate nuclei information related mainly to the contralateral visual field. The projections from these structures might play an important role in regulating transmission of visual information in the retinotopically distinct parts of each dorsal lateral geniculate nucleus. By contrast, the projections from the modulatory nuclei of the pontomesencephalic tegmentum are likely to contribute to the functional synchronization of both dorsal lateral geniculate nuclei during the sleep-wakefulness cycle and saccadic eye movements.

Velocity response profiles of collicular neurons: parallel and convergent visual information channels.

We have recorded from single neurons in the retinorecipient layers of the superior colliculus of the cat. We distinguished several functionally distinct groups of collicular neurons on the basis of their velocity response profiles to photic stimuli. The first group was constituted by cells responding only to photic stimuli moving at slow-to-moderate velocities across their receptive fields (presumably receiving strong excitatory W-type input but not, or only subthreshold, Y-type input). These cells were recorded throughout the stratum griseum superficiale and stratum opticum and constituted 50% of our sample. The second group of cells exhibited excitatory responses only at moderate and fast velocities (presumably receiving excitatory Y-type but not W-type input). These cells constituted only about 7% of the sample and were located principally in the lower stratum griseum superficiale. The third group of cells was constituted by cells excited over the entire range of velocities tested (1-2000 /s) and presumably received substantial excitatory input from both W- and Y-channels. These cells constituted almost 26% of our sample and were located in the lower stratum griseum superficiale, stratum opticum and the upper part of the stratum griseum intermediale. Overall, cells receiving excitatory Y-type input, i.e. the sum of group two and group three cells, constituted about a third of the sample and their excitatory discharge fields were significantly larger than those of cells receiving only W-type input. A fourth distinct group of collicular neurons was also constituted by cells responding over a wide range of stimulus velocities. These cells were excited by slowly moving stimuli, while fast-moving photic stimuli evoked purely suppressive responses. The excitatory discharge fields of these cells (presumably, indicating the spatial extent of the W-input) were located within much larger inhibitory fields, the extent of which presumably indicates the spatial extent of the Y-input. These low-velocity-excitatory/high-velocity-suppressive cells were recorded from the stratum griseum superficiale, stratum opticum and stratum griseum intermediale and constituted about 17% of the sample. The existence of low-velocity-excitatory/high-velocity-suppressive cells in the mammalian colliculus has not been previously reported. Low-velocity-excitatory/high-velocity-suppressive cells might play an important role in activating "fixation/orientation" and "saccade" premotor neurons recorded by others in the intermediate and deep collicular layers. Overall, in the majority (57%) of collicular neurons in our sample there was no indication of a convergence of W- and Y-information channels. However, in a substantial minority of collicular cells (about 43% of the sample) there was clear evidence of such convergence and about 40% of these (low-velocity-excitatory/high-velocity-suppressive cells) appear to receive excitatory input from the W-channel and inhibitory input from the Y-channel.

Intravitreal injection of TGFbeta induces cataract in rats.

PURPOSE: In a previous study, it was determined that TGFbeta induces cataractous changes in the rat lens in vitro. The purpose of the present study was to determine whether the introduction of biologically active TGFbeta into the vitreous stimulates cataractous changes in the rat lens in situ. METHODS: TGFbeta was injected into the vitreous of the left eye of anesthetized adult male Wistar rats. The right eye received sterile vehicle as a control. Three to four months after injection, animals were killed, and lenses were enucleated and examined for cataractous changes. RESULTS: All lenses from control eyes remained transparent and maintained normal cellular architecture throughout. In contrast, lenses from TGFbeta-injected eyes displayed cloudiness in the cortex. In some lenses, distinct opacities were also apparent at the equator and extending some distance toward the anterior and posterior poles. Histologically, the opacities corresponded to subcapsular plaques containing aberrant cells and accumulations of extracellular matrix. In addition, cortical fibers in the anterior and posterior of all lenses displayed variable degrees of swelling, and many retained their nuclei. In some regions, the fiber cells appeared to have degenerated to form large homogeneous areas. The cellular architecture of the equator of these lenses was also disrupted and, in the most severe case, no bow zone was apparent with nucleated cells extending to the posterior pole. CONCLUSION: The introduction of active TGFbeta into the vitreous induced lenses to undergo cataractous changes. In addition to the TGFbeta-induced changes in the epithelium that were reported previously, cataractous changes observed in this study also involved the lens fiber cells and resembled changes observed in human posterior subcapsular and cortical cataracts.

Cortical plasticity revealed by circumscribed retinal lesions or artificial scotomas.

We review the work of others in which the effects of circumscribed, topographically corresponding binocular retinal lesions on the topographic organization of the visual cortex revealed that there is a substantial degree of topographical plasticity in the primary visual cortices of adult cats and macaque monkeys. Despite the evidence indicating that the reorganization of the topographic map in primary visual cortices of adult cats and macaques related to the input from one eye could be suppressed for a long time by inputs related to the other eye, we observed a substantial degree of topographical plasticity in the primary visual cortices of adult cats in which we have made circumscribed monocular retinal lesions. Overall, in both binocularly and monocularly lesioned adult animals, most cells recorded in the cortical projection zone of the retinal lesion (LPZ), several hours, several weeks or several months after placement of the lesions exhibited 'ectopic' excitatory visual receptive fields (RFs) which were displaced to the normal retina in the immediate vicinity of the lesion. The presence of ectopic RFs in cells recorded in the cortical LPZ, combined with the presence of normal cortical representation of the part of the retina in the vicinity of the lesion, indicate a clear expansion of the cortical representation of the part of the retina surrounding the lesion. When stimulated via the ectopic RFs, cortical cells exhibited normal orientation tuning and in the case of animals with monocular lesions, the orientation tuning of binocular cells when stimulated via ectopic RFs appeared to be very similar to that when the cells were stimulated via the RFs in the normal, unlesioned eye. In both binocularly and monocularly lesioned animals, the responses evoked by optimal visual stimuli from the ectopic RFs were substantially weaker than those evoked from their normal counterparts. Similarly, upper velocity limits were significantly lower when visual stimuli were presented via the ectopic RFs. In contrast to cats in which the retinal lesions were made in adulthood, in cats lesioned monocularly in adolescence (8-11 weeks postnatal), both the peak discharge rates and upper velocity limits of responses to photic stimuli presented via the ectopic RFs were very similar to those to stimuli presented via the normal eye. The intracortical mechanism(s) underlying the long-term cortical plasticity revealed by retinal lesions are likely to be closely linked to the mechanism(s) underlying the short-term reversible enlargement of cortical receptive fields observed with artificial scotomas. Furthermore, a similar putative intracortical mechanism(s) appears to underlie psychophysical phenomena observed in studies of retinal scotomas in humans. Overall, the research reviewed here strongly challenges the view that receptive fields of neurons in mammalian visual cortices are 'hard-wired'.

Areas PMLS and 21a of cat visual cortex are not only functionally but also hodologically distinct.

In several cats, paired visuotopically matched injections of retrogradely transported fluorescent dyes, diamidino yellow (DY) and fast blue (FB), were made into two visuotopically organized, functionally distinct extrastriate cortical areas, the posteromedial lateral suprasylvian area (PMLS area) and area 21a respectively. After an appropriate survival time, the numbers of thalamic, claustral and cortical cells which were single-labelled with each dye as well as the numbers of cells in these structures labelled with both dyes (double-labelled cells) were assessed. The clear majorities of thalamic cells projecting to PMLS area (DY labelled cells) and to area 21a (FB labelled cells) were located in the ipsilateral lateral posterior-pulvinar complex with smaller proportions located in the laminae C and the medial intralaminar nucleus of the ipsilateral dorsal lateral geniculate nucleus and several nuclei of the rostral intralaminar thalamic group. Despite the fact that DY labelled (PMLS-projecting) and FB labelled (area 21 a-projecting) cells in all thalamic nuclei were well intermingled, only 1-5% of retrogradely labelled thalamic cells projected to both areas (cells double-labelled with both dyes). Small proportions of retrogradely labelled cells were located in the ipsilateral and to a lesser extent the contralateral dorsocaudal claustra. The proportions of claustral neurons retrogradely labelled with both dyes varied from 4 to 9%. Over half of the cortical neurons labelled retrogradely from area 21a or PMLS area were located in the supragranular layers of the ipsilateral area 17, with smaller proportions located in the supragranular layers of the ipsilateral areas 18 and 19 and even smaller proportions located in mainly but not exclusively, the infragranular layers of the ipsilateral areas 21b and 20a. Again despite strong spatial intermingling of neurons labelled with DY and these labelled with FB, the proportions of associational cortical neurons double-labelled with both dyes were small (2 to 5.5%). Finally, small proportions of neurons retrogradely labelled with DY or FB were located, mainly but not exclusively, in the supragranular layers of the contralateral areas 17, 18, 19 and 21a. Again, the proportions of the double-labelled neurons in the contralateral cortices were small (1-4.5%). Thus, the present study indicates that despite the fact that the diencephalic and telencephalic inputs to the visuotopically corresponding parts of area 21a and PMLS area originate from the same nuclei, areas and layers, the two areas receive their afferents from the largely separate populations of neurons.