Reorganization of visual pathways following posthatching removal of one retina in pigeons

Organization of visual pathways was studied in 2-month-old pigeons that underwent unilateral retinal removal on either the day of hatching (ERA, i.e., early retinal ablated) or the 9th day after hatching (LRA, i.e., late retinal ablated). A general size reduction of visual areas contralateral to the removed retina was found in ERA pigeons, which additionally showed an altered differentiation of thalamic visual targets as well as a different cytoarchitectonic arrangement of the superficial layers of the optic tectum. No comparable modifications were found in LRA pigeons. The retinal projections of the remaining eye were studied following intraocular injections of 3H-proline. Both in ERA and LRA pigeons, the distribution of retinofugal afferents to primary visual regions contralateral to the injected eye was similar to that of control pigeons. Anomalous ipsilateral projections from the remaining retina to primary retinorecipient regions were found in ERA pigeons only. Effects of early ablation of one retina on second-order visual connections were also studied. Following injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the visual Wulst contralateral to the operated eye, a smaller number of ipsilateral projecting thalamo-Wulst neurons was found as compared with control pigeons. In contrast, the contralateral thalamo-Wulst projections were increased. No changes in thalamo-Wulst projections were found following tracer injections into the opposite Wulst, i.e., ipsilateral to the operated eye. The present study demonstrates a substantial anatomical reorganization of both primary and secondary visual pathways following unilateral retinal removal immediately after hatching, when maturation of the visual system is not yet completed.     

Localization of Nogo and its receptor in the optic pathway of mouse embryos

We have investigated the localization of Nogo, an inhibitory protein acting on regenerating axons in the adult central nervous system, in the embryonic mouse retinofugal pathway during the major period of axon growth into the optic chiasm. In the retina, Nogo protein was localized on the neuroepithelial cells at E12 and at later stages (E13-E17) on radial glial cells. Colocalization studies showed expression of Nogo on vimentin-positive glia in the retina and at the optic nerve head but not on most of the TuJ1- and islet-1-immunoreactive neurons. Only a few immature neurons in the ventricular and peripheral regions of the E13 retina were immunoreactive to Nogo. In the ventral diencephalon, Nogo was expressed on radial glia, most strongly on the dense radial glial midline raphe within the chiasm where uncrossed axons turn and in the initial segment of the optic tract. In vitro studies showed that the Nogo receptor (NgR) was expressed on the neurites and growth cones from both the ventral temporal and dorsal nasal quadrant of the retina. In the optic pathway, NgR staining was obvious in the vitreal regions of the retina and on axons in the optic stalk and the optic tract, but not in the chiasm. These expression patterns suggest an interaction of Nogo with its receptor in the mouse retinofugal pathway, which may be involved in guiding axons into the optic pathway and in governing the routing of axons in the optic chiasm.     

Morphological properties of chick retinal ganglion cells in relation to their central projections

Morphological properties of chick retinal ganglion cells (RGCs) were studied in relation to their central projections in 23 chicks. A total of 217 RGCs were retrogradely labeled by applying a carbocyanine dye (DiI) to the thalamus and optic tectum. The labeled RGCs were classified into six groups on the basis of their somal areas, dendritic fields, and branching patterns. The dendrites of these RGCs extended horizontally in the inner plexiform layer (IPL) forming eight dendritic strata. The RGCs in each group showed certain specificities in their central projections. Group Ic predominantly projected to the tectum. Groups IIs and IIIs showed a high thalamic dominance. Groups Is and IIc were nonspecific with regard to their tectal and thalamic projections. Group IVc showed tectal‐specific projections. Occurrence rates of the dendritic strata increased progressively toward the inner part of the IPL, i.e., DSs (dendritic strata) 1–4 were scantily distributed, DSs 5 and 6 were moderately distributed, and DSs 7 and 8 were the most frequently distributed. A total of 42 dendritic stratification patterns were identified, and of these, 18 patterns were common to the tectal RGCs (tec‐RGCs) and thalamic RGCs (tha‐RGCs). The common patterns were detected very frequently in the tec‐ and tha‐RGCs (≈85%), and the dendritic strata were largely distributed in the inner part of the IPL (DSs 5–8). In contrast, the remaining 24 noncommon stratification patterns showed low occurrence rates (≈15%); however, these dendritic strata were widely distributed in both the outer (DSs 1–4) and inner (DSs 5–8) IPL. J. Comp. Neurol. 514:117–130, 2009. © 2009 Wiley‐Liss, Inc.     

The growth-inhibitory protein Nogo is involved in midline routing of axons in the mouse optic chiasm

We have investigated the role of Nogo, a protein that inhibits regenerating axons in the adult central nervous system, on axon guidance in the developing optic chiasm of mouse embryos. Nogo protein is expressed by radial glia in the midline within the optic chiasm where uncrossed axons turn, and the Nogo receptor (NgR) is expressed on retinal neurites and growth cones. In vitro neurite outgrowth from both dorsonasal and ventrotemporal retina was inhibited by Nogo protein, and this inhibition was abolished by blocking NgR activity. In slice cultures of the optic pathway, blocking NgR with a peptide antagonist produced significant reduction in the uncrossed projection but had no effect on the crossing axons. This result was confirmed by treating cultures with an anti-Nogo functional blocking antibody. In vitro coculture assays of retina and optic chiasm showed that NgR was selectively reduced on neurites and growth cones from dorsonasal retina when they contacted chiasm cells, but not on those from ventrotemporal retina. These findings provide evidence that Nogo signaling is involved in directing the growth of axons in the mouse optic chiasm and that this process relies on a differential regulation of NgR on axons from the dorsonasal and ventrotemporal retina.     

Evaluation of the influence of optic stalk melanin on the chiasmatic pathways in the developing rodent visual system.

In a number of mammalian species, fibre outgrowth in the developing retinofugal pathway is coincident with the presence of melanin in the retinal part of the optic stalk. The presence of melanin is transient in this developing system and has been proposed to play a role in the guidance of retinofugal fibres. Further, it has been suggested that this stalk melanin accounts for the differences between the size of the uncrossed retinal component in pigmented and nonpigmented strains. However, a recent study showed that there is no melanin in the optic stalk of Manchester rats during fibre outgrowth. Since such rats supposedly have a normal pigment distribution and a normal pattern of decussation at the optic chiasm, this finding appears to undermine the suggested role played by stalk melanin in establishing the laterality of retinal fibre projections in other mammalian species. The aim of this study was to re-evaluate the relationship between melanin in the stalk and the development of the retinofugal pathway in three strains of rat: the Wild type, Long Evans Hooded, and the Albino. The Albino rat, which lacks melanin-bearing cells entirely, was shown to have the smallest uncrossed projection, approximately 1,340 ipsilaterally projecting cells (ipc), whereas the Long Evans (2,760 ipc) and the Wild-type strain (2425 ipc) were found to have a larger uncrossed retinal component. In both pigmented strains, melanin was restricted to the eye cup and absent from the optic stalk throughout all stages of development.(ABSTRACT TRUNCATED AT 250 WORDS)     

Visual-field-specific heterogeneity within the tecto-rotundal projection of the pigeon.

The organization of the tecto-rotundal projection of the pigeon was investigated by means of anterograde and retrograde tracing techniques. Besides the known organization in tecto-rotundal connectivity, this study additionally demonstrates major variations in the ascending projections of different tectal subfields. We show that the ventral tectum opticum (TO) has significantly more projections onto the nucleus rotundus (Rt) than dorsal tectal areas. This difference coincides with differential innervation densities of afferent fibres within rotundal subregions. While ventral tectal efferents project onto the ventral and central Rt, dorsal tectal efferents mainly arborize within limited areas between the central Rt and its dorsal cap, the nucleus triangularis. Thus, the ventral TO, representing the lower and frontal field of view, exhibits a quantitatively and spatially enhanced projection onto the Rt, as compared with the dorsal TO. The data presented here demonstrate a visual field-dependent projection pattern of ascending tectal outputs onto different rotundal domains. The data are consistent with behavioural studies, demonstrating tectofugal lesions to suppress visual stimulus analysis mainly within the frontal field of view.     

The effects of early prenatal monocular enucleation on the routing of uncrossed retinofugal axons and the cellular environment at the chiasm of mouse embryos

Whereas it has been shown that early monocular enucleations produce a reduction in the uncrossed pathway from the surviving eye in rats and ferrets, similar evidence for binocular interactions in the development of the uncrossed component in mice is currently open to question. Using retrograde tracing, we have investigated the time course of changes in the uncrossed retinofugal pathway immediately after the early prenatal monocular enucleation in mouse embryos. Removal of one eye from C57 pigmented mice at embryonic day (E) 13 does not cause a reduction of the earliest uncrossed component from the central retina examined 1 day later at E14. However, a substantial reduction of the uncrossed pathway is seen at E15, the time when the major uncrossed projection first arises from the ventral temporal retina. This reduction is greater in E16 one-eyed embryos, indicating that most retinal axons from the ventral temporal retina rely on a binocular interaction for their turning at the chiasm. Further, early removal of one eye at E13 does not produce any obvious changes in the cytoarchitecture of RC-2-immunopositive radial glia at the chiasm, nor of the stage-specific antigen-1 (SSEA-1) -expressing neurons. This lack of changes in the cellular organization at the chiasm indicates that the reduction of the uncrossed pathway is probably produced by an elimination of binocular fibre interactions at the chiasm, rather than through a degenerative change of cellular elements at the chiasm as a consequence of the eye removal procedure.     

Regional distribution of catecholaminergic terminals in the pigeon visual system

A glyoxilic acid histofluorescence technique was used in this study to determine the distribution of catecholaminergic (CA) terminals in the pigeon visual areas. Our results show that the main visual structures are under the influence of CA nuclei of the brain stem. In particular, the pigeon Wulst, like the mammalian visual cortex, is profusely innervated by CA terminals. In fact, dense CA afferents, most likely noradrenergic (NA) terminals, were found in the hyperstriatum intercalatus superior and the nucleus intercalatus hyperstriati accessorii; area which represent the terminal zone of the retino-thalamo-hyperstriatal pathway. These results suggest a possible convergence of NA terminals and visual fibers on common target cells in the Wulst.     

Spatial organization of the pigeon tectorotundal pathway: an interdigitating topographic arrangement

The retinotectofugal system is the main visual pathway projecting upon the telencephalon in birds and many other nonmammalian vertebrates. The ascending tectal projection arises exclusively from cells located in layer 13 of the optic tectum and is directed bilaterally toward the thalamic nucleus rotundus. Although previous studies provided evidence that different types of tectal layer 13 cells project to different subdivisions in Rt, apparently without maintaining a retinotopic organization, the detailed spatial organization of this projection remains obscure. We reexamined the pigeon tectorotundal projection using conventional tracing techniques plus a new method devised to perform small deep-brain microinjections of crystalline tracers. We found that discrete injections involving restricted zones within one subdivision retrogradely label a small fraction of layer 13 cells that are distributed throughout the layer, covering most of the tectal representation of the contralateral visual field. Double-tracer injections in one subdivision label distinct but intermingled sets of layer 13 neurons. These results, together with the tracing of tectal axonal terminal fields in the rotundus, lead us to propose a novel "interdigitating" topographic arrangement for the tectorotundal projection, in which intermingled sets of layer 13 cells, presumably of the same particular class and distributed in an organized fashion throughout the surface of the tectum, terminate in separate regions within one subdivision. This spatial organization has significant consequences for the understanding of the physiological and functional properties of the tectofugal pathway in birds.     

Retinotopic organization of central optic projections in Rana pipiens

The retinotopic organization of the anuran visual system has been investigated with the method of selective anterograde transport of horseradish peroxidase (HRP) following retinal lesions. The course of optic axons to specific structures was also confirmed by retrograde transport in the optic tract following HRP injections in the tectum and pretectum. As the optic nerve reaches the optic chiasm, the fibers from each of the four retinal quadrants appear as bands with the nasal (n) quadrant entering the chiasmal anterior pole, followed by ventral (v), temporal (t), and dorsal (d) quadrants. The preoptic nucleus is the first structure to be innervated, followed by the suprachiasmatic nucleus; both are innervated directly from fibers in the dorsal part of the optic nerve, which contains fibers from all the retinal quadrants. Each quadrant expands across the dorsoventral extent of the chiasm at the point where it enters. At this level the quadrants are arrayed along the rostrocaudal axis (as they are later in the marginal optic tract) in the sequence n-v-t-d. Optic fibers then spread across the chiasm, the nasal quadrant splits, taking up positions in the rostral and caudal margins of the optic radiation. Following the split in the nasal representation, the optic tract is transformed into topographically arranged sheets in the marginal optic tract. In the other retinorecipient nuclei, the sheet of optic axons is transformed back into the shape of the retinal hemisphere. Topographic maps of this kind display one of two possible orientations: (1) in the tectum and the nucleus lentiformis mesencephali (nLM), the temporal retina is represented in the anterior portion of the nucleus, whereas the nasal quadrant is found in the posterior portion; (2) in the thalamus, the retinotopic map is organized as a mirror-image reversal of that seen in the tectum and nLM (i.e., the nasal pole is anterior, whereas the temporal pole is in the posterior portion of the nucleus). Structures with this type of retinal map include the rostral visual nucleus, the corpus geniculatum, the nucleus of Bellonci, and the posterior thalamic nucleus. A third type of innervation occurs in the nucleus of the basal optic root (nBOR), which is the only mesencephalic visual nucleus not innervated by the marginal optic tract. The basal optic root is formed by the fibers exiting most caudally from the optic chiasm. All the retinal quadrants contribute to the basal optic root, but no evidence of retinotopy was found in nBOR.4+ target nuclei.     

Neuroactive substances in the developing dorsomedial telencephalon of the pigeon (Columba livia): Differential distribution and time course of maturation

The avian hippocampal formation has previously been shown to contain many of the same neurotransmitters and related enzymes that are found in mammals. In order to determine whether the relatively delayed development of the mammalian hippocampus is typical of other vertebrates, we investigated the maturation of a variety of heuroactive substances in the hippocampal formation of the homing pigeon. The distribution of two transmitter-related enzymes, choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), the neurotransmitter GABA, and four neuropeptides (substance P, enkephalin, neuropeptide Y, and somatostatin) was studied by immniunohistochemistry in the developing hippocampal complex. The pattern and/or the time course of changes in the distribution of immunoreactivity varied among the different neuroactive substances examined. Immunoreactivity to ChAT and TH was found exclusively in fibers and terminal-like processes, whereas GABA and peptide immunoreactivity was seen in cells and neuropil. Quantitative differences in the density, number, and size of stained cells were assessed by a computer-assisted image analyzer. For the majority of the substances, developmental patterns in the distribution of immunoreactivity differ between the hippocampus proper and the area parahippocampalis, the two major areas that together make up the avian hippocampal complex. The adult pattern of immunoreactivity was generally attained by 3 weeks after hatching. For many of the neuroactive substances found in cell bodies, there was a gradual decrease in the density of immunoreactive cells with a concomitant increase in the density of immunoreactive neuropil. The actual number of stained cells usually increased to a peak at 9 days posthatching and then declined until 3 weeks posthatching, when the adult value was reached. These results are discussed in relation to the advantages that the pigeon hippocampal complex may provide in the study of developmental processes. Parallels with the distribution of the same neuroactive substances in the mammalian hippocampus are used to suggest possible functional similarities between the avian and mammalian hippocampal regions. © 1994 Wiley-Liss, Inc.     

Distribution of neuropeptide Y, substance P, and choline acetyltransferase in the developing visual system of the pigeon and effects of unilateral retina removal.

The distribution of three neuroactive substances, neuropeptide Y, substance P, and choline acetyltransferase, was studied by immunocytochemical methods in central visual regions of adult, developing, and ablated pigeon brains. In normal adult brains, neuropeptide Y-positive cells and processes were present in the nucleus pretectalis, the nucleus of the basal optic root, the nucleus of the marginal optic tract, and the visual Wulst. Substance P-positive cells and processes were found in the optic tectum and in the visual Wulst. Stained fibers and terminal-like processes, but no cells, were also observed in several visual thalamic nuclei. Choline acetyltransferase-positive cells and processes were located in the optic tectum, visual Wulst, the nucleus isthmo opticus, nucleus isthmi and certain visual thalamic nuclei. Cholinergic fibers and processes, but no cells, were present in the nucleus principalis precommissuralis, the supraoptic decussation, and the nucleus lentiformis mesencephali, pars magnocellularis. In the course of development, the distribution of immunoreactivity for all three substances was found to vary. These changes often involved either progressive increases or decreases in the density of labeled cells, neuropil and/or terminal-like profiles. Experiments with retina ablated pigeons clearly demonstrated that changes in the normal pattern of immunoreactivity distribution only occurred if the retina was removed immediately after hatching, i.e., before retinofugal connections have been established. The adult pattern of immunoreactivity for all three substances appears to be reached at about the same time that the anatomical and functional maturation of the pigeon visual system is completed. The present results suggest that this temporal correlation reflects the important role that retinal afferents play in the development of these putative peptidergic and cholinergic systems.     

An electrophysiological study of early retinotectal projection patterns during optic nerve regeneration inHyla moorei

The sequence of regeneration of the optic nerve into the tectum has been studied using electrophysiological visual mapping in the frog,Hyla moorei. Some individuals were remapped to confirm the sequential nature of the changes described. The projection was retinotopic throughout regeneration. Multiunit receptive field sizes were initially large but progressively decreased to normal over approximately 30 days. The differences between these results and earlier studies are discussed.     

GABA-like immunoreactivity of neurons in the chicken diencephalon and mesencephalon

The chick brain is a useful model system for studying the ontogeny and phylogeny of neural circuitry, especially that of the visual system. In this study the distribution of cells and processes showing GABA-like immunoreactivity (GABA+) in the diencephalon and mesencephalon of the posthatch chick was determined immunohistochemically with a polyclonal antibody to GABA and compared with the results of similar studies in mammals. Most of the small GABA+ cells were found in the chick visual centers such as the nucleus lateralis anterior, suprachiasmatic nucleus, ventral lateral geniculate, optic tract, dorsolateralis anterior pars lateralis, lentiformis mesencephali, ectomammillary nucleus, area pretectalis, and the optic tectum. Large GABA+ cells were found in the following nuclei: reticularis superior, posteroventralis thalami, subpretectalis, isthmi pars magnocellularis, interstitio-pretectosubpretectalis, mesencephalicus lateralis pars dorsalis. These large cell-containing nuclei receive projections from visual or auditory centers. GABA+ axons were found throughout the diencephalon and mesencephalon but were especially prominent in the ansa lenticularis, fasciculus medialis longitudinalis, and optic tract. The distribution of GABA+ cells in the chick is more widespread than in rodents and exhibits an increased association with the visual centers suggesting a correlation with the specialized visual requirements of the bird.     

The functional roles of feedback projections in the visual system

Neurons in the nervous system make connections with ascending feedforward projections and descending feedback projections, as well as projections from neural structures at the identical hierarchical level. These neurons form extremely complicated neural networks and pathways. Compared with the role of the feedforward projection, much less is known concerning the functional roles of the feedback projection. Visual cortex is a good model for studying functional roles of cortical feedback projections which involve many high functions, such as attention, searching and cognition. The present review mainly focused on the functional roles of feedback projections in the visual system.     

Experimentally induced enlargement of the uncrossed retinotectal pathway in rats

The present experiments investigate the effects of neonatal lesions upon projection patterns of the uncrossed retinotectal pathway in albino rats. The results indicate that enlargement of the terminal field from one eye can be induced either by a contralateral optic tract lesion or by removal of the opposite eye at birth. The extent of the enlargement is more prominent in the latter case. If an optic tract lesion is accompanied by eye enucleation on the side ipsilateral to the tract lesion, the uncrossed retinotectal projection from the remaining eye will undergo further enlargement. However, optic fiber counts show that such an enlargement of the terminal field is not due to a significant increase in the number of uncrossed optic axons which contribute to the enlarged projection, but rather to an increased terminal arbor of individual axons (as shown by results from fiber counts). While a severe ganglion cell loss was observed in the retina contralateral to a tract lesion, a substantial population of cells persists in the ganglion cell layer and the number of cells appears much higher than the number of uncrossed optic axons arising from the same eye. The implications of these findings are discussed in relation to results reported in previous studies.     

Two distinct populations of tectal neurons have unique connections within the retinotectorotundal pathway of the pigeon (Columba livia)

The tectofugal pathway is a massive ascending polysynaptic pathway from the tectum to the thalamus and then to the telencephalon. In birds, the initial component of this pathway is known as the tectorotundal pathway; in mammals, it is known as the tectopulvinar pathway. The avian tectorotundal pathway is highly developed; thus, it provides a particularly appropriate model for exploring the fundamental properties of this system in all amniotes. To further define the connectivity of the tectorotundal projections of the tectofugal pathway, we injected cholera toxin B fragment into various rotundal divisions, the tectobulbar projection, and the ventral supraoptic decussation of the pigeon. We found intense bilateral retrograde labeling of neurons that stratified within layer 13 and, in certain cases, granular staining in layer 5b of the optic tectum. Based on these results, we propose that there are two distinct types of layer 13 neurons that project to the rotundus: 1) type I neurons, which are found in the outer sublamina of layer 13 (closer to layer 12) and which project to the anterior and centralis rotundal divisions, and 2) type II neurons, which are found in the inner sublamina of layer 13 (closer to layer 14) and which project to the posterior and triangularis rotundal divisions. Only the labeling of type I neurons produced the granular dendritic staining in layer 5b. An additional type of tectal neuron was also found that projected to the tectobulbar system. We then injected Phaseolus vulgaris-leucoagglutinin in the optic tract and found that the retinal axons terminating within tectal layer 5b formed narrow radial arbors (7–10 μm in diameter) that were confined to layer 5b. Based on these results, we propose that these axons are derived from a population of small retinal ganglion cells (4.5–6.0 μm in diameter) that terminate on the distal dendrites of type I neurons. This study strongly indicated the presence of a major bilateral oligosynaptic retinotectorotundal pathway arising from small retinal ganglion cells projecting to the rotundus with only a single intervening tectal neuron, the proposed type I neuron. We suggest that a similar organization of retinotectopulvinar connections exist in reptiles and in many mammals. J. Comp. Neurol. 387:449–465, 1997. © 1997 Wiley-Liss, Inc.     

Electrophoretic analysis of specific proteins in the regenerating goldfish retinotectal pathway

Proteins in the goldfish retinotectal pathway were analyzed by 2-D gel electrophoresis, under conditions of optic nerve crush or eye removal. A specific cluster of proteins was detected, consisting of 4 components, all of which are highly concentrated in the intact optic nerve. Two components were not detectable in non-visual areas of the goldfish brain. The total cluster was diminished by about 80% in the denervated optic tectum, and its level was restored during optic nerve regeneration. These data were interpreted as evidence for visual system-specific proteins in the goldfish retinotectal pathway.