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M Constantine-Paton

Publications and source records attributed to M Constantine-Paton.

69 records · Page 4Linked to original sources
PubMed1983

The organization of the fibers in the optic nerve of normal and tectum-less Rana pipiens.

We have examined the detailed order of retinal ganglion cell (RGC) axons in the optic nerve and tract of the frog, Rana pipiens. By using horseradish peroxidase (HRP) injections into small regions of the retina, the tectum, and at various points along the visual pathway, it has been possible to follow labelled fibers throughout their course in the nerve and tract. Several surprising features in the order of fibers in the visual pathway were discovered in our investigation. The fascicular pattern of RGC axons in the retina is similar to that described in other vertebrates; however, immediately central to their entry into the optic nerve head, approximately half of the fibers from the nasal or temporal retina cross over to the opposite side of the nerve. Although the axons from the dorsal and ventral regions of the retina generally remain in the dorsal and ventral regions of the nerve, some fiber crossing occurs in those axons as well. The result of this seemingly complex rearrangement is that the optic nerve of Rana pipiens contains mirror symmetric representations of the retinal surface on either side of the dorsal ventral midline of the nerve. The fibers in each of these representations are arranged as semicircles representing the full circumference of the retina. This precise fiber order is preserved in the nerve until immediately peripheral to the optic chiasm, at which point age-related axons from both sides of the nerve bundle together. Consequently, when a small pellet of HRP is placed in the chiasmic region of the nerve, an annulus of retinal ganglion cells and a corresponding annulus of RGC terminals in the tectum are labelled. As the age-related bundles of fibers emerge from the chiasm they split to form a medial bundle and a lateral bundle, which grow in the medial and lateral branches of the optic tract, respectively. Although the course followed by RGC axons in the visual pathway is complex, we propose a model in which the organization of fibers in the nerve and tract can arise from a few rules of axon guidance. To determine whether the optic tecta, the primary retinal targets, play a role in the development and organization of the optic nerve and tract, we removed the tectal primordia in Rana embryos and examined the order in the nerve when the animals had reached larval stages. We found that the order in the nerve and tract was well preserved in tectumless frogs. Therefore, we propose that guidance factors independent of the target direct axon growth in the frog visual system.

Animals↗
PubMed1983

Trajectories of axons in ectopic VIIIth nerves.

Transplantation of the acousticolateral placode to the evacuated eye position in embryos of the frog Rana pipiens has been used to force axons of the VIIIth cranial nerve to penetrate the diencephalon. These ectopic axons establish a growth trajectory that is strikingly similar to their normal growth trajectory within the medulla oblongata despite the fact that no other axons within the diencephalon normally follow this route. The result is discussed in terms of the "blueprint" and substrates pathway hypotheses which have been advanced to explain the initial development of axon tracts within the central nervous system.

Animals↗
PubMed1983

Qualitative and quantitative measures of plasticity during the normal development of the Rana pipiens retinotectal projection.

We have examined the following aspects of retinal development in the frog, Rana pipiens: (1) the overall pattern of cell addition to the retina; (2) the relative rate of retinal ganglion cell (RGC) accretion; and (3) the changes in RGC density during larval development. In addition, we have studied the development of the retinal projection onto the tectum by means of the anterograde transport of horseradish peroxidase (HRP) and measurements of the volume of tectal neuropil at several larval stages and in postmetamorphic frogs. We find that the addition of new cells to the retina of Rana pipiens larva is restricted to the ciliary margin and that this addition is concentric at all larval stages. Additionally, the morphometric measures of retinal and tectal growth, along with the HRP histochemistry, indicate that the retinal projection exhibits considerable plasticity during normal development. The plasticity we observe in normal development may explain why the retinotectal projection can compensate its area and volume in experimental paradigms that effect drastic changes in innervation density.

Animals↗
PubMed1982

A banded distribution of retinal afferents within layer 9A of the normal frog optic tectum.

A banded distribution of retinal ganglion cell axons within layer 9A of the superficial tectal neuropil in Rana pipiens was revealed through anterograde labeling with horseradish peroxidase. Layer 9A previously has been demonstrated to mediate binocular vision through a polysynaptic pathway by way of the nucleus isthmi. This nucleus interconnects analogous regions of the two tectal lobes such that isthmic axons retinotopically map the visual world of the ipsilateral eye within tectal layers 9A and 8. Thus, we have found that a pattern of retinal ganglion cell bands occurs in binocular regions of normal frogs. This pattern is similar, but not identical, to the experimentally produced stripes previously observed in the doubly innervated tecta of 3-eyed and single tecta frogs. Qualitative and quantitative comparisons of these two types of afferent segregation patterns have implicated several structural and functional parameters which might be involved in band formation.

Animals↗
PubMed1981

Topographic and morphometric effects of bilateral embryonic eye removal on the optic tectum and nucleus isthmus of the leopard frog.

Rana pipiens were raised through metamorphosis after extirpation of both eye primordia at Shumway embryonic stage 17 (Shumway '40). The visual connections between the isthmic nuclei and the optic tectum were examined in these animals using horseradish peroxidase (HRP) histochemistry. Isthmo-tectal projections are normally aligned with the primary retinotectal map. We asked whether these connections would develop normal topographic organization in the absence of normal retinal input. HRP was formed into a solid pellet (congruent to 200-500 micrometer diameter) and inserted into one tectal lobe on the tip of a fine metal probe. The procedure produced relatively restricted retrograde label in somas and dendrites in both isthmi nuclei. In the nucleus isthmus ipsilateral to the tectal lobe receiving the HRP pellet, processes of tecto-isthmi neurons were labeled by anterograde transport. The topography of the isthmo-tectal and tecto-isthmic projections were identical in the developmentally enucleated animals and in normal frogs, even though eye removal severely reduced the volume of the optic tecta and the isthmi nuclei. Thus our analyses indicate that retinal contacts do not play an active role in the development of the positional or polarity cues that are involved in "mapping" projections between central visual nuclei. These results are discussed in the context of peripheral specification of central connections and in terms of models that have recently been proposed to explain the development of the retinotectal system.

Animals↗
PubMed1981

Anatomy and physiology of experimentally produced striped tecta.

Transplantation of a third eye primordium to the forebrain region of a frog (Rana pipiens) embryo causes two retinal projections to converge on a single tectal lobe. These projections form stereotyped eye-specific termination bands (Constantine-Paton, M., and M. I. Law (1978) Science 202: 639-641) that are similar to the source-specific stripes found normally in many regions of the mammalian brain. In the present study, we use quantitative analyses of anatomical data and double labeling techniques to demonstrate that induced bands of three-eyed frogs are approximately 200 micrometers wide, that they invariably run in a rostrolateral to caudomedial direction, and that they represent interdigitating synaptic zones which fill the entire superficial neuropil of the dually innervated tectal lobe. This periodic segregation pattern is not seen in the superinnervated diencephalon or in the optic tracts. Morphometric measurements on animals with dually innervated tectal lobes revealed an approximate 30% hyperplasia that was restricted largely to the deeper predominantly cellular tectal layers. Each of the banded retinal projections occupied neuropil volumes that were roughly 50% smaller than the volume occupied by the noncompeting retina of the same animal. Eye-specific segregation was detected with extracellular recording techniques as an ability of one of the two eyes to elicit consistently more and larger action potentials throughout a radial penetration of the superficial tectal neuropil. In several preparations, electrolytic lesions confirmed that physiologically defined positions of eye dominance corresponded to a band from the same eye. Maps of the visual field projections within dually innervated tecta were relatively normal and their orientation was consistent with the initial embryonic orientation of the retinas. Eye laterality, time of arrival, or fasciculation during growth are not responsible for this induced banding. Instead, our results are attributed to two mechanisms that are probably fundamental to neural mapping. These are: differential affinities between retinal and tecta loci which normally align the projection by bringing together appropriate pre- and postsynaptic areas and interactions among retinal ganglion cell fibers. The latter causes axons from physically neighboring retinal ganglion cell bodies to terminate together within the tectum and consequently increases the internal order of map. We propose that these same two mapping mechanisms may be responsible for the afferent segregation found in diverse regions of many vertebrate brains.

Animals↗
PubMed1980

Right and left eye bands in frogs with unilateral tectal ablations.

Surgical ablation of a single tectal lobe in Rana pipiens can cause regenerating retinal ganglion cell axons to cross to the remaining tectum. These synaptically deprived fibers can obtain termination space in a retinotopic and highly stereotyped manner. Each of the two eyes can share the undisturbed tectum by terminating in mutually exclusive, eye-specific stripes that alternate across the medial-lateral extent of the tectal lobe. Invading axons from the ipsilateral eye must actively displace established synapses from the contralateral eye in order to form these exclusive termination zones because the normal projection to the intact tectum is not severed in these experiments. In animals in which a large proportion of anomalous fibers do not reach the undisturbed tectum, only a few ipsilateral eye bands are observed. Nevertheless, these bands have the same width, periodicity, and orientation as those observed in fully banded preparations. When ipsilateral eye terminal density is extremely low, banding is absent. The completely striped termination pattern of unitectal animals is identical to the pattern previously reported in the dually innervated tecta of three-eyed R. pipiens. We theorize that this pattern results from a compromise between two synaptogenic forces that are active in regeneration as well as in development.

Animals↗
PubMed1978

Eye-specific termination bands in tecta of three-eyed frogs.

An extra eye primordium was implanted into the forebrain region of embryonic Rana pipiens. During development both normal and supernumerary optic tracts terminated within a single, previously uninnervated tectal lobe. Autoradiographic tracing of either the normal or supernumerary eye's projection revealed distinct, eye-specific bands of radioactivity running rostrocaudally through the dually innervated tectum. Interactions among axons of retinal ganglion cells, possibly mediated through tectal neurons, must be invoked to explain this stereotyped disruption of the normally continuous retinal termination pattern.

Animals↗
PubMed1976

Axonal guidance of developing optic nerves in the frog. I. Anatomy of the projection from transplanted eye primordia.

Right or left eye primordia of Shumway stage 16-18 Rana pipiens embryos were transplanted to the position normally occupied by the ear, where they developed into externally normal eyes. Ganglion cell density in the retina of the transplanted eye was significantly lower than the ganglion cell density in the animal's normal eyes. No significant difference was observed between normal and transplanted inner and outer nuclear layers. In several preparations a large piece of embryonic forebrain was included in the initial eye graft. Optic nerves from the transplanted eyes penetrated this transplanted forebrain and established a dorsocaudal growth trajectory relative to the ectopic tissue's original anterior-posterior and dorsal-ventral axes. After traversing the forebrain, the transplanted optic nerve fibers penetrated the medulla where they invaraibly grew dorsocaudally to take up and maintain a dorsolateral position in the white matter of the spinal cord. The consistent dorsocaudal trajectory established by the translocated optic tract in the ectopic forebrain and in the hindbrain and spinal cord is very similar to the growth trajectory in the normal diencephalon, suggesting that dorsocaudal growth relative to the three major axes of the neural tube is an inherent property of optic nerve fibers. These results also suggest that the polarity cues which guide normal optic tract growth are not unique to the diencephalic regions of the neural tube.

Animals↗
PubMed1976

Axonal guidance of developing optic nerves in the frog. II. electrophysiological studies of the projection from transplanted eye primordia.

When a primordial eye was transplanted to the ear position in Rana pipiens embryos, the optic nerve from the ectopic eye penetrated the medulla and invariably established a tract in the dorsolateral white matter of the ipsilateral spinal cord. In response to visual stimulation of the transplanted eye, extracellular recordings with metal microelectrodes were conducted with the spinal cords of post-metamorphic animals. Visual activity in the spinal cord could only be recorded in those experimental animals in which the transplanted optic nerve succeeded in penetrating the medulla. This activity was frequently encountered in the gray matter of the cord well below the dorsolateral position of the transplanted optic tract. The discharge characteristics and adaptation properties of the visual activity were often similar to that of optic nerve fibers from normal eyes suggesting that axons or their collaterals branch off from the transplanted optic tract and arborize within the spinal cord. However, occassionally stimulation of the transplanted eye evoked activity with adaptation and/or response characteristics unlike that of normal optic nerve fibers. Visual activity in the spincal cords of our experimental animals could be driven by moving small dark objects within circumscribed regions in the visual field of the transplanted eye. However we were unable to find any evidene of a systematic mapping of the transplanted retina within these abnormally penetrated spinal cords.

Adaptation, Physiological↗
PubMed1975

Central projection of optic tract from translocated eyes in the leopard frog (Rana pipiens).

In Rana pipiens embryos, eye anlagen were moved to the evacuated ear position, where they continued to differentiate and sent their optic nerve fibers into the hindbrain. Upon entering the medulla, the optic fibers turned caudally, penetrated the spinal cord, and traversed the dorsolateral white matter to the caudal end. We found this pattern of growth in every animal; the optic fibers did not enter the tecta. These results suggest the existence within the neural tube of a three-dimensional gradient system to which embryonic optic fibers are responsive and which may guide the normal development of the visual pathway.

Animals↗
PubMedDate not supplied

A cell surface molecule distributed in a dorsoventral gradient in the perinatal rat retina.

Brain topography may have its earliest expression as spatial gradients of molecules controlling the deposition of neurones and neuronal processes. In the vertebrate visual system there is evidence that the stereotyped alignment of central retinal projections relies on an initial spatially organized distribution of molecules in both the retina and its central target nuclei. We used an immunological approach to look for molecules that are so organized and produced a monoclonal antibody (JONES) which shows a pronounced dorsal to ventral gradient of binding in the rat retina throughout the period when retinal ganglion cell axons are forming topographically organized projections within the central nervous system (CNS). Binding is present throughout the radial thickness of the retinal epithelium in regions where postmitotic neurones are generated but is not associated with any consistent histological characteristic of the tissue. The antibody was shown to bind on the cell surface of freshly dissociated retinal cells, and dorsal retinal quadrants were found in vitro to have nearly twice as much antigen as ventral retinal quadrants. Initial biochemical characterization of the target epitope reveals that it is a lipid present in chloroform/methanol extracts from perinatal retina and is sensitive to neuraminidase digestion.

Animals↗