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Retinotectal Specificity: Chemoaffinity Theory
... The functional view is less fortunate in this respect. However, it must be emphasized that the major functional assumption that starkly contrasts the structural and the functional perspectives is unequivocally supported by neurophysiological evidence and is shared by all current neuroscientific theories (e.g., Anderson, Silverstein, Ritz, & Jones, 1977;Arbib, 1980;Edelman, 1978;John, 1967John, , 1972Kachalsky, Rowland, & Blumenthal, 1974;Sperry, 1976;Uttal, 1978). This assumption is that cognition is a transient phenomenon created by the functioning of distributed components of the nervous system. ...
... Weiss's resonance principle is no longer generally accepted by developmental neuroscientists. But we believe his ideas concerning indiscriminate synaptic connectivity, successfully challenged by Sperry and his associates (see Attardi & Sperry, 1960, 1963Meyer & Sperry, 1976), must be distinguished from his suggestive element-implulse specificity hypothesis, which has yet to be directly tested. ...
... 47). In fact, it is still not clear that a resolution between Sperry's directional connectionism and Weiss' element-impulse specificity model has yet been achieved (see Meyer & Sperry, 1976;Sperry, 1966;Wall, 1966;Weiss, 1966). As Wall (1966) argued, "the so-called specificity of neuronal function ... may mean that specificity of function can be attained without a microscopic determination of the exact morphological structure of some parts of the nervous system" (p. ...
Bibliography: leaves 65-73 Supported in part by the National Institute of Education under contract no. HEW-NIE-C-400-76-0116
... B, C Optic tectum (TeO) showing contralateral fibres entering the superficial layer of the superficial white and gray zone (SWGZ) (arrowed), four sublaminae of the SWGZ with a few fibres projecting into the Deep White Zone (DWZ). Scale bars= 125/am Sperry 1976) may also work in association with structural cues (Horder and Martin 1978) or a combination of both (Scholes 1981). The premise that retino-recipient nuclei receive input from specific sub-populations of retinal ganglion cells may be also influenced by these factors. ...
Cobaltous-lysine is transported anterogradely from the optic nerve of the teleost, Lethrinus chrysostomus (Lethrinidae, Perciformes). The marginal optic tract is labelled in longtitudinal bands of light and dark staining fibres which persists caudally within the ventral division but not in the dorsal division. This species possesses multiple central targets in the contralateral preoptic, diencephalic, pretectal, periventricular and tectal regions of the brain. In addition, a greater subdivision of the marginal optic tract is found to project to various nuclei. Ipsilateral projections are found in the suprachiasmatic nucleus and in the region of the horizontal commissure. Projections are also found in the telencephalic region of the nucleus olfactoretinalis and the thalamic region of the nucleus thalamoretinalis. The retinotopicity of some of these nuclei, found in previous studies, is discussed in relation to the possibility of specific sub-populations of retinal ganglion cells having different central targets.
... The cellular interactions that establish the precisely ordered pattern of retinotectal connections, as well as the consistent alignment and overall extent of the map, must operate in the context of this extremely dynamic synaptic readjustment . Shifting connections thus argue against theories of retinotectal map formation that postulate the existence of fixed cytochemical labels that specify connections by allowing synapse formation only between retinal and tectal cells with corresponding labels (Sperry, 1963; Meyer and Sperry, 1976). During normal development, such cell-specific " labels " would have to change continuously as the projection shifts its position caudally. ...
Interconnecting neuronal populations in the vertebrate CNS are typically not well matched in their overall topographic patterns of histogenesis and differentiation during development. One striking example of this mismatch is the retinotectal system of the frog, where the retina grows in concentric annuli, while the optic tectum, a major retinal target, adds new neurons at only the caudo-medial border. The retinal ganglion cell (RGC) terminals nevertheless form an organized map in the tectum during the period when the two structures are undergoing such disparate modes of growth. This led Gaze et al. (Gaze, R. M., M. J. Keating, and S. H. Chung (1974) Proc. R. Soc. Lond. (Biol.) 185: 301-330) to propose that the terminals must shift caudally during development. In the present study, we have directly tested the hypothesis of "shifting connections" by selectively labeling an identified population of RGC terminals, those at the optic nerve head (ONH), and determining their tectal projection site relative to a particular group of [3H]thymidine-labeled tectal neurons. With this double-label technique, we have found that RGC terminals from cells at the ONH move from a position rostral to the [3H]thymidine-labeled tectal cells to a position caudal to these same cells during the latter half of larval development. This represents a movement of approximately 1.4 mm across the tectal surface between stages T&K XII and T&K XXV. In addition, we have used electron microscopy and electrophysiology to demonstrate that the RGC terminals make functional synaptic connections during this period. This indicates that RGC terminals continually change the tectal neurons with which they form functional synapses during the development of the retinotectal system. We propose that such moving, but highly ordered connections can best be explained by a two stage mechanism for map formation, in which graded selective adhesions between cells in appropriate regions of retina and tectum provide the overall gross retinotopy of the projection, while competitive interactions between RGC terminals are responsible for the refinement of the precision in this system.
Cambridge Core - Philosophy of Science - What Biological Functions Are and Why They Matter - by Justin Garson
Neurogenesis begins with the formation of a simple tube whose walls consist of a few thousand undifferentiated cells. The embryo accomplishes the remarkable feat of transforming the neural tube within a few weeks into the most intricate precision instrument ever created, the central nervous system. How does it do this? At the beginning, the mechanisms at its disposal are not different from those used for the formation of other organs. Morphogenetic processes, such as evagination, produce first the three brain vesicles—fore-, mid-, and hindbrain—then the optic vesicles in the telencephalon; they are transformed into optic cups by invagination. When the optic vesicle contacts the overlying epidermis, it induces a thickening, the lens placode, which invaginates and forms the crystalline lens. Further caudal, another placode (the otic placode) is induced that invaginates and is detached from the epidermis, like a lens. This vesicle, called the otocyst, undergoes complicated morphogenetic transformations leading to the formation of the semicircular canals and cochlea of the inner ear. The several billion neurons are produced by ordinary cell divisions. Those in the neural tube occur near the lumen of the central canal, the so-called ventricular zone. Following their last mitotic division, they migrate radially to the outer part of the tube, where they settle down and arrange themselves in the lamina, brain nuclei, columns, and reticular formations that represent the cytoarchitecture of the central nervous system. At this time, or even earlier the cytodifferentiation of neurons and glia begins. The differentiation of neurons is distinct from that of other cell types because of two features: (a) the production of a prodigious variety of neuron types differing from each other in many structural and biochemical characteristics, in contrast to the uniformity of bone or muscle cells; and (b) the capacity to spin out protoplasmic processes, the axons and dendrites. The axons follow stereotyped pathways and form the intracentral tract systems and peripheral nerve patterns. Eventually they establish synapses or sensory terminations at their targets.
The concepts “prespecification” and “plasticity” are often ill-defined: to make them useful, exact criteria as well as the stage of development to which they are applied have to be stated precisely. For instance, plasticity often refers to functional adaptation. But our discussion will deal only with structural modifiability. The term “prespecification” conveys the notion that a developmental process, or phenotypic characteristics of a particular neuron strain, are irreversibly programmed or determined from an early stage on. The neural tube which gives rise to the entire central nervous system represents an early stage. One can inquire whether the undifferentiated neural tube of a 2-day chick embryo has acquired already the regional specification for cervical, brachial, thoracic, lumbar sectors which can be characterized by several criteria in later stages. One widely used test for specification is the transplantation experiment borrowed from general experimental embryology. If prospective brachial and cervical or brachial and thoracic segments are exchanged in the 2-day neural tube, they differentiate according to their site of origin, rather than the site of implantation, as shown, for instance, by the presence or absence of a lateral motor column in the transplant (B. Wenger, 1951). Another criterion would be the circuitry for coordinated limb movements which develops only at limb levels. Transplantation of the brachial neural tube to the lumbar level in 2-day chick embryos results in the performance of synchronus leg movements akin to wing flapping. Alternating movements were never observed; hence segmental specification defined by this criterion is also fixed at that stage (Narayanan and Hamburger, 1971).
For its proper operation, the nervous system depends on extremely specific interconnections between neurons, and between neurons and peripheral end-organs. Obviously, the specificity of connections requires a high degree of control during development. The initial steps in the establishment of connections involve the formation and proper positioning of the neurons (histogenesis, see Chapter 5). Next, the neurons must elaborate their axons and dendrites and form connections between the two. This chapter, together with Chapter 7, considers the mechanisms of the latter processes.
G. E. Coghill (1929) attempted to describe the sequence of steps involved in the differentiation of the central nervous system of ambystoma following his careful observations upon the development of their walking and swimming behaviors. The central premise of his work was that the development and elaboration of behavior patterns was the manifestation of an orderly sequence of steps of differentiation in the embryonic nervous system (Hamburger, 1963).
This review of findings in brain research is concerned with the biological causes of perception.
The ordered representation of the retina in the tectum of hamsters can be influenced by experimental manipulation of factors intrinsic to the developmental process, such as the direction and timing of arrival of retinal fibers. The orientation of the retinotopic map in the tectum with respect to the neural axes, the amount of representation of retinal subareas on the tectal surface, and the laminar specificity of retinal terminals in tectum are differentially affected by these developmental factors.
If the amount of tectal tissue is reduced at birth in hamster by a large amount, only a portion of visual field comes to be represented. The area of visual field represented is in every case lower nasal visual field, regardless of whether caudal, rostrolateral, central, or superficial tectal tissue is removed. This asymmetry in surface representation is also reflected in the laminar distribution of retinal fibers in the tectum. A source for the inhoniogeneity in visual field representation may be direction of optic tract arrival in tectum, which begins at the rostrolateral margin of the tectum, where lower nasal visual field is represented.
The polarity of the retinotopic map in tectum—its orientation with respect to the neural axes—may be dissociated from direction of fiber arrival, for if fibers are induced to enter the tectum medially, opposite to their normal entry point, a retinotopic map of normal order and polarity develops. Classes of mechanisms that account for both of these observations are discussed.
The eyes of amphibians, both anurans and urodelans, have interested students of development since the beginning of the twentieth century. Spemann investigated the roles of the optic vesicle and surface ectoderm in lens formation (Spemann, 1903, 1905, 1907, 1912, 1938) before he began his better known studies on neural induction and the “organizer.” In the United States, W. Lewis (1904, 1907a, b) and Harrison (1920, 1929) also employed this system of lens induction in their work on dependent and independent development. Mangold (1931) wrote a very complete review of the experiments on amphibian eyes up to that time. These early investigations consisted of the following types of microsurgical experiments: 1. isolating the prospective lens-forming ectoderm by removing the eye-forming region of the neural plate or the optic vesicle, 2. combining optic vesicle and ectoderm of different prospective significance located in other regions of the head or flank, and 3. transplanting the prospective lens ectoderm to other parts of the body. Several different species were employed and these were found to differ in the ability of the prospective lens ectoderm to differentiate into a lens without an eyecup and in the capacity of the optic vesicle to induce a lens from foreign ectoderm. Additional investigations seemed to indicate that these properties varied inversely in different species and led Spemann (1938) to propose the hypothesis of “double assurance” in lens formation. This concept postulates two processes, each of which can lead to lens development under experimental conditions: 1. self-differentiation of prospective lens ectoderm, and 2. lens induction by the optic vesicle. In normal development, these two mechanisms reinforce each other. In a later section of this account, it will be seen how recent investigations have led to refinements in our knowledge of the interactions leading to the development of a lens in its proper relation to the eyecup.
A considerable part of developmental brain research is concerned with how cellular mechanisms of perception are built. This chapter attempts a review of the field, but does not claim to cover all complex issues brought to light. There is good reason to be selective, as there are difficult conceptual problems. First, we must define perception so that this psychological function—the uptake of information by sensory systems—can be related to the many developmental processes that contribute to it. Somehow we must compare selective and organizing processes in perception with pattern-making and pattern-using systems in the growth of the entire behavioral system: body and brain.
The branch of neuroscience seeking relationships between the structural development of the sensory systems and the emergence of their function is still in its infancy. Although such relationships have been found, current knowledge is restricted to simple generalizations about functional capacities, such as the onset of vision or the onset of audition, and the most obvious of structural changes, such as the formation of synaptic connections between the eye or the ear and the brain. The inability to show more complicated relationships is due in part to difficulties in testing a wide variety of sensory functions in immature animals and in part to the subtlety of many of the developmental changes in the structure of neurons. Accordingly, this chapter is divided into two sections, the first focusing on anatomical structure and the second on function, both physiological and perceptual.
Processing of the visual image in the brain requires an orderly relay of information between the various visual centers. This is accomplished by having these visual centers interconnect in very precise patterns. A good example of this is the projection of the retinal ganglion cells to the brain. The axons of the ganglion cells course along a well-defined tract, enter only very specific nuclei in the brain, and within these nuclei terminate in a retinotopic fashion such that neighboring retinal ganglion cells terminate in neighboring areas of the central visual nuclei. A major problem in developmental neurobiology is to determine how these patterns of connections develop. The transplantation technique affords one method by which to study this problem.
A common misunderstanding of the selected effects theory of function is that natural selection operating over an evolutionary time scale is the only function-bestowing process in the natural world. This construal of the selected effects theory conflicts with the existence and ubiquity of neurobiological functions that are evolutionary novel, such as structures underlying reading ability. This conflict has suggested to some that, while the selected effects theory may be relevant to some areas of evolutionary biology, its relevance to neuroscience is marginal. This line of reasoning, however, neglects the fact that synapses, entire neurons, and potentially groups of neurons can undergo a type of selection analogous to natural selection operating over an evolutionary time scale. In the following, I argue that neural selection should be construed, by the selected effect theorist, as a distinct type of function-bestowing process in addition to natural selection. After explicating a generalized selected effects theory of function and distinguishing it from similar attempts to extend the selected effects theory, I do four things. First, I show how it allows one to identify neural selection as a distinct function-bestowing process, in contrast to other forms of neural structure formation such as neural construction. Second, I defend the view from one major criticism, and in so doing I clarify the content of the view. Third, I examine drug addiction to show the potential relevance of neural selection to neuroscientific and psychological research. Finally, I endorse a modest pluralism of function concepts within biology.
It is well established that many fibre tracts in the nervous system are topographically organized. But how are such projections built up during ontogenesis? In this article G. Rager focuses on the development of the retino-tectal connection in the chick as a paradigm for the sequence of developmental events in higher vertebrates.
Unsuccessful axonal regeneration in frog or goldfish spinal cord is thought to be due in part to inappropriate denervated synaptic sites attracting regenerating axons as they pass by the lesion zone (Bernstein and Bernstein, '69; Bernstein and Gelderd, '73). The reported success of optic nerve regeneration in these same animals may result because there are no inappropriate synaptic sites available to the regenerating axons. To test for this we denervated areas within thalamus and mesencephalon which lie along the path of regenerating optic axons to determine whether or not abnormal connections would form in these areas and affect the success of optic nerve regeneration. After transection of the brainstem through the isthmal region, terminal degeneration was found in several zones adjacent to optic nerve targets or the optic tract (i.e., nucleus rotundus, corpus geniculatum laterale, and torus semicircularis). In adult frogs receiving left isthmal transection, we also crushed the right optic nerve and then examined the regenerated optic projection at intervals up to six months after nerve crush using anterograde transport of 3H-proline. In no instance did the regenerating optic axons alter their distribution within visual neuropil zones or invade those areas deafferented by the isthmal lesion. Histological study showed that the axons cut by the isthmal lesion did not regenerate back to their sites to prevent the invasion of optic axons into these zones. We then attempted to force optic axons into foreign territory by removing a major projection zone, the optic tectum. With tectal ablation and isthmal transection, regenerating optic axons were offered synaptic space made available by both lesions. However, we found abnormal optic projections only in the middle and posterior thalamic neuropil and in the remaining tectal hemisphere. Optic axons did not expand into any of the areas deafferented by the isthmal transection, even though some of them were further denervated by the tectal ablation. We conclude that optic axons will not invade non-optic areas deafferented by an isthmal lesion even if a large number of optic axons have no normal target to innervate.
The development of the trout optic nerve is quantitatively described from early ontogenesis into adulthood. The nerve is oval in cross section until stage 34, thereafter the formation of vertically aligned parallel folds can be observed and thus the unique shape of a folded ribbon is gradually attained. Quantitative measurements revealed a linear increase in cross sectional area, caused in part by the formation of new folds and in part by an increase in size of the preexisting ones. We attribute the continuous expansion of individual folds to an increase in fiber size subsequent to myelination rather than to the addition of new fibers. The total number of glial cells increased concomitantly per fold.
Myelinogenesis starst at stage 33 with the ensheathement of axons beginning at the dorsal edge of the primary fold and follows a highly ordered pattern throughout development, strictly succeeding neural outgrowth. The functional significance of this pattern is discussed.
The course of functional recovery of vision during the compression of the retinotectal projection that follows hemitectal ablations was mapped by behavioral methods in goldfish (Carassius auratus). Differential suppression of respiration to red or green stimuli was used as a behavioral measure. Results show that vision was restored throughout the temporal half-field, originally blinded by tectal lesion, within 84 to 112 days of surgery. The scotoma diminished in an orderly fashion, starting from the central edge and progressing caudalward. Color discriminability was concomitant with visual recovery. The return of color vision indicates prespecification of retinal and tectal cells for color and selective reconnection of neurons according to their specificities. Functional topographic reorganization of the retinotectal projection implies that locus-specific affinities between retinal and tectal neurons, which may play a prominent role in the direction of nerve growth and formation of synapses under more normal circumstances, are not permanently fixed even in mature goldfish and may yield to compensatory developmental pressures created by the size disparity.
We have traced fiber tracts in the regenerating teleost spinal cord and have found that the regenerative capabilities of fiber tracts coming from different parts of the CNS vary considerably. Some descending tracts can regenerate up to 5.6 mm beyond a transection, while other fiber tracts cannot even penetrate the scar tissue. In spite of a great disturbance of their normally ordered pathways as they grow through the lesion site, those tracts which can regenerate can find their appropriate funiculi in the distal spinal cord.
Redirected growth of the optic tract in hamsters with lesions of the midbrain tectum at birth results in anomalous retinal projections with correlated functional effects; these include a sparing of visually elicited turning responses which are lost after comparable lesions in adulthood. However, the animals sometimes overshoot or undershoot the target, and the responses are slow to be completed. In cases of early unilateral lesions, an optic tract projection to the wrong side of the midbrain is correlated with turning in the wrong direction in response to stimuli in specific locations. These misdirected movements can be enhanced by reward or suppressed by non-reward, or abolished by surgical section of the abnormal pathway in the mature animal. Principles derived from the experiments with animals allow us to predict that specific lesions in fetal and neonatal humans will cause particular patterns of altered growth of neuroanatomical pathways. These alterations can be expected to cause behavioral anomalies, not only in sensorimotor functions, but also in cognitive functions and in emotional responses and expression; some neuropsychological findings can be interpreted in this manner.
The detailed morphology of neurons in the optic tectum of the common goldfish, Carassius auratus, was reinvestigated using rapid Golgi and Golgi-Cox methods. Neurons were classified initially on the basis of the orientation of the primary dendritic processes within the tectum: vertical, horizontal and non-oriented. These 3 groups were subdivided according to the shape of the soma and the axonal and dendritic configurations.The cell types observed in the present study were compared with those reported in earlier analyses of the goldfish optic tectum. Numerous differences, primarily of soma location and axonal origin and pathway for each cell type, were found. The structure of the goldfish optic tectum appears to be quite similar to the tectum of other teleosts.
During the normal course of development of the rodent cerebellum, the adult one-to-one relationship between climbing fibres and Purkinje cells is preceded by a transient stage of multiple innervation. In this article, the mechanisms involved in the regression of the supernumerary synapses are considered in the light of results obtained from strains of mutant mice and X-irradiated rats in which the development of the cerebellum is abnormal. The role of this regressive process in the post-natal shaping of olivocerebellar connections is also analysed and compared to another example of developmental elimination of supernumerary connections.
A small piece of tissue in the neural tube of Xenopus laevis was cut out and either replaced in the same embryo after rotating it by 180 degrees, or transplanted into another embryo. We show that, within 24 h after fertilization, the neural tube consists of a mosaic of regions, each with a fixed tendency to develop into a specific part of the nervous system. If a piece of tissue is grafted into another embryo, a pre-determined structure is formed without reference to its surroundings. If a piece of tissue is rotated by 180 degrees, the neural structures resulting from it are correspondingly reversed. Despite such determination of the anatomical polarity, the polarity for selective nerve connections remains labile. When a part or the whole of the tectum is reversed, the trajectory of the optic nerve is sometimes altered, but the array of optic axons invading the tectum ignores the anatomical reversal of the target structure and forms a normal retino-tectal projection with respect to the whole animal. Whenever the position of the diencephalon relative to the tectum is altered, however, the axial polarity of the retino-tectal projection is altered correspondingly.
Neuromuscular specificity has been investigated in chick embryos with a grafted supernumerary leg. The nerves of the lumbar plexus are divided between the two legs so that rostral nerves innervate the grafted leg and the caudal nerves supply the host's original leg. The basic topographic organization of the histologically definable motor neuron clusters of the lateral motor columns remains unchanged by the addition of a supernumerary leg. Intramuscular injections of identified leg muscles have been used to map the intraspinal location of specific motor pools in stage 38 (12-day) embryos. In the normal embryo, the gastrocnemius muscle is innervated by neurons in a central dorsal cluster of motor neurons in segments 26-29. In six experimental cases, the motor neurons supplying the gastrocnemius muscle of a rostrally placed grafted leg were consistently located in a specific medial cluster of neurons in segments 23-25. Motor neurons in this location never normally innervate a gastrocnemius muscle, even in the very young embryos during the period of naturally occurring cell death. This observation of a systematic mismatch between a particular motor cluster and an abnormally innervated muscle indicates the operation of a selective developmental process. A hierarchy of selective chemoaffinities may best explain our experimental results.
An abnormal, ipsilateral projection was formed by deflecting optic fibers that normally innervate the posterior part of one tectum into the anterior end of the opposite tectum. When anterior recipient tectum was simultaneously denervate, the deflected fibers formed a retinotopic map in this region that was reversed with respect to the anterior-posterior tectal axis.
Alterations in normal retinotectal topography by mechanical disruption of fiber passage during development was studied in Syrian hamsters using both neuroanatomical and electrophysiological techniques. The mechanical block to fiber passage was created with a medial to lateral slit across the superior colliculus on the day of birth. At maturity, topographically aberrant projections were found in areas of residual scar tissue. These aberrant projections were synaptically functional, producing neurons with mutiple, spatially separated visual receptive fields.No evidence was found for an orderly compression of the retinotopic map in the tectum consequent to the transitory blockage of fiber passage.
An eye-in-water electrophysiological recording method was used to map accurately the retinotectal projection of normal goldfish, and the results were compared with those obtained using the more customary technique of recording with the eye in air. In air, the receptive fields were found not only enlarged, as expected from the extreme myopia, but were also shifted toward the periphery by as much as 25°, resulting in a sizable deficit in the map. In view of this mapping error, the eye-in-water technique was used to reinvestigate the projection plasticity previously found with the eye-in-air recording method. After ablation of the posterior half-tectum or medial quartertectum, with and without optic nerve crush, recordings were obtained in 40 fish, 1 to 18 months postsurgically. The results substantially confirmed that compression, whereby the visual field, including regions surgically deprived of their normal target zones, comes to project onto the tectal remnant in compressed retinotopic fashion, but the compression found was not homogeneous and as complete as previously thought. Rather, the degree of compression was greatest near the lesion and progressively decreased toward the opposite tectal pole where it was frequently absent. This compression difference between these tectal regions was typically a factor of two and in early postsurgical stages as great as three to four. In addition, regions of the peripheral field corresponding to the tectal lesion were found to be missing from the recorded projection even after long survival times. Some projection anomalies, not previously seen, were also observed. These findings have implications for theories on the growth of selective nerve connections.
Tritiated thymidine was injected intraperitoneally into juvenile goldfish that were 3 to 6 cm in body length. After 6 h to 32 months these fish were then killed for autoradiography of retina and tectum. The autoradiographs indicated that despite the maturity of these goldfish both retina and tectum were still growing by the accretion of new cells at their margins. As was shown for Xenopus, new retinal cells were added around the entire retinal circumference, while new tectal cells were added principally around the posterior tectal margin and none to the anteriormost edge. However, goldfish of this size have a well-defined and functional retinotopic projection of retina onto tectum. This means that newly created ganglion cells of temporal retina, destined to send axons to anterior tectum, will find only old tectal cells at their target locus with which to connect. Presumably preexisting retinal terminals in the tectum must be shifted posteriorly to allow the new ganglion cells to find tectal synaptic sites.
In goldfish, one eye was enucleated, and after two or more weeks a select fraction of optic fibers from the remaining eye was deflected into the ipsilateral optic tectum. At varying intervals, the optic reinnervation of the ipsilateral tectum was measured by autoradiography and electrophysiologic mapping. Both methods indicated the deflected optic fibers not only innervated the appropriate region of tectum but also spread beyond this, occupying a total area that was several times greater than normal. Correlated with this spreading were low grain density in the autoradiograms and reduction in the number of amplitudes of units recorded electrophysiologically. The electrophysiology also revealed this projection to be almost devoid of topographic organization, showing only a crude but appropriate polarity.
In adult goldfish the nasal half-retina from one eye and the temporal half-retina from the other eye were removed, followed by left tectal ablation. Visuotectal projections were later mapped electrophysiologically. The contralateral half-retina projected to the entire tectum and showed expansion of the visual field; the projection was orderly. Partially superimposed projections from the temporal half-retina of one eye and the nasal half-retina from the other eye were found in the middle of the tectum, whereas the rostral and caudal tectum were innervated exclusively by the appropriate half-retina. When temporal half-retinae from two eyes were ablated along with left tectal removal, some animals showed expansion of the contralateral half-retinal field onto the tectum; however, in other animals the ipsilateral projection innervated the tectum either partially or completely and the projections from two eyes were superimposed in mirror-image fashion.The results are discussed in relation to the mechanisms controlling selective fiber regeneration with underlying fiber-to-fiber interactions.
During specification of orderly neural maps, axons correctly navigate to their targets and form terminal arbors in topographically correct positions. To learn more about this mapping process, the patterns of geniculocortical topography were correlated with growth of axon arbors in the hamster visual cortex. Topography was studied by retrograde transport of WGA-HRP from area 17 to the dorsal lateral geniculate nucleus (LGd) and visualized with TMB histochemistry. In separate experiments, geniculocortical axon arbors were filled with HRP deposited extracellularly into the optic radiations and stained with cobalt-intensified DAB.
On the day of birth (P0) and on P1–2, a crude topography was detected in the geniculocortical system. At these ages, geniculocortical axons coursed in the embryonic white matter of the visual cortex, parallel to the pia. During their passage, multiple short collaterals, with no terminal arbors, were extended into the subplate and deeper portions of the cortical plate. By P3–5, the topography was more precise and simple axonal arbors had now begun to be formed on some branches within the cortical plate. During the second postnatal week, branches in the white matter without terminals were eliminated and the ramifications of branches in the gray matter became more elaborate. The arbors continued to increase in complexity and resembled adult forms by P24.
It is still unclear how the retinotectal map of the chick is formed during development. In particular, it is not yet known whether or not the organization of fibres plays a role in the formation of this map. In order to contribute to the solution of this problem, we analysed the representation of the retinal topography at closely spaced intervals along the fibre pathway. We injected HRP into various sites of the tectal surface and traced the labelled fibre bundles back to the retina. The retinal topography was reconstructed at ten different levels, i.e. in the retina, the optic nerve head, the middle of the optic nerve, the chiasm (three levels), the optic tract (three levels), and the optic tectum. We obtained the following results: (1) The labelled fibre bundles as well as the fields of labelled retinal ganglion cells were always well delimited and coherent. (2) The reconstructions show that transformations of the retinal topography occur in the fibre pathway. The first and most important transformation is found in the optic nerve head where the retinal image is mirrored across an axis extending from dorsotemporal to ventronasal retina. In addition, the retinal representation is split in its temporal periphery. Thus, central and centrotemporal fibres are no longer in the centre of the image but close to the dorsal border of the nerve. Peripheral fibres are found along the medial, ventral and lateral circumference of the nerve. In the optic tract a second transformation occurs. The retinal topography is rotated clockwise by about 90 degrees and flattened to a band. The flattening is accompanied by a segregation of fibre bundles so that eventually central and centrotemporal retinal fibres are located centrally, ventral fibres dorsally and dorsal retinal fibres ventrally in the tract. By these two transformations an organization of fibres is produced in the optic tract which can be projected onto the tectal surface without major changes given that dorsal and ventral fibres remain in their relative positions, and that deep lying fibres project to the rostral and central tectum, superficial fibres to the caudal tectum. The transformations which we have observed follow specific rules and thus maintain order in the pathway although retinotopy is lost. In conjunction with our earlier studies on the development of the retinotectal system we conclude that fibres are laid down in a chronotopic order. The transformations take place under particular structural constraints.(ABSTRACT TRUNCATED AT 400 WORDS)
Retinal axons of Xenopus tadpoles at various stages of larval development were filled with horseradish peroxidase (HRP), and their trajectories and the patterns of branching within the tectum were analyzed in whole-mount preparations. To clarify temporal and spatial modes of growth of retinal axons during larval development, special attention was directed to labeling a restricted regional population of retinal axons with HRP, following reported procedures (H. Fujisawa, K. Watanabe, N. Tani, and Y. Ibata, Brain Res. 206:9–20, 1981; 206:21–26, 1981; H. Fujisawa, Dev. Growth Differ 26:545–553, 1984).
In developing tadpoles, individual retinal axons arrived at the tectum, without clear sprouting. Axonal sprouting first began when growing tips of each retinal axon had arrived at the vicinity of its site of normal innervation within the tectum. Thus, the terminals of the newly added retinal axons were retinotopically aligned within the tectum. The retinotopic alignment of the terminals may be due to an active choice of topographically appropriate tectal regions by growth cones of individual retinal axons.
The stereotyped alignment of the newly added retinal axons was followed by widespread axonal branching and preferential selection of those branches. Each retinal axon was sequentially bifurcated within the tectum, and old branches that had inevitably been left at ectopic parts of the tectum (owing to tectal growth) were retracted or degenerated in the following larval development. The above mode of axonal growth provides an adequate explanation of cellular mechanisms of terminal shifting of retinal axons within the tectum during development of retinotectal projection. Selection of appropriate branches may also lead to a reduction in the size of terminal arborization of retinal axons, resulting in a refinement in targeting.
The proximal stump of a transected mandibular nerve was grafted onto the rostrodorsal surface of the optic tectum in adult Rana pipiens to investigate the morphologic characteristics of nonspecific axonal regeneration in a highly organized region of central nervous system (CNS). Within the first 3 weeks postgraft surgery (WPS), the nerve-tectum interface became firmly established. Concomitant with this was an invasion of the host tectum by a small number of fine “pioneerlike” axons from the nerve. By 6 WPS there developed a concerted instreaming of a large number of peripheral fibers. Once within the CNS, the foreign axons distributed themselves throughout the rostrocaudal extent of the tectum, but primarily its dorsal aspect within superficial layers 8 and 9.
Presence of intact optic fibers at the time of mandibular fiber invasion served somewhat to restrict the regenerating aberrant axons in their course through layer 9. This restriction could be avoided by removal of the optic input either before or during peripheral ingrowth. However, once peripheral fibers had entered and established themselves in the host environment, no subsequent manipulation of the retinotectal projection had any effect.
The aberrant growth pattern, which appeared remarkably stable after 6 WPS, consisted of a plexus of medium- and fine-caliber peripheral axons. Many of these fibers had numerous branches and “en passant” varicosities, the latter encompassing a variety of shapes and sizes. Terminal swellings and arborizations were also found.
When comparing the regeneration of optic and mandibular nerve fibers in the tectum, two distinctions were made. Whereas optic axons revealed a fascicular and layered organization, mandibular axons showed a highly segregated and disordered growth pattern. These characteristic differences were maintained even when the two fiber systems were allowed to coregenerate into the same target tectum. Thus, each of the two groups of axons interacts with the tectal substrate in a distinct manner, apparently independent of the other.
Through anatomical and physiological studies of the regenerating retinotectal projection of goldfish, we sought to determine whether the establishment of a topographic projection is attained through a refinement of an initially less precise pattern of innervation. A 1-mm-wide mediolateral strip of caudal tectum was removed so that a small island of tectal tissue was spared at the caudal pole, and the contralateral nerve was either crushed (TIX) or left intact (TI). The presence of regenerated axons in the ablated zone and the reinnervation of the caudal island were assessed with anterograde and retrograde labeling methods in the following postoperative intervals: early, 20-50 days; middle, 50-110 days; and late, more than 170 days. The anterograde radioautographic method revealed that the appropriate layers of the tectal island became reinnervated by optic axons during the early period. During the middle and late periods, one to several large, discrete bundles bridging the lesion zone along the surface of exposed subtectal structures were readily identified both by radioautography and by anterograde or retrograde labeling following application of horseradish peroxidase to the transected optic nerve or tectal island, respectively. In contrast, the anterograde horseradish peroxidase method did not reveal axon bundles extending caudal to the half-tectum in the absence of a tectal island. Among TIX cases, retrograde horseradish peroxidase labeling of the contralateral nasal retina was more widespread in the middle period than in the late period, a result we interpret as reflecting an improvement in topographical precision with time. The area of retinal labeling among TIX cases in the late period was similar to that following caudal tectal injection in cases with simple nerve crush, although it was still elevated above normal control values. Physiological maps indicated a focal representation of the nasal retina in the tectal island in both periods and did not reveal a transient extreme convergence of retinal input. These findings are discussed in relation to Sperry's chemoaffinity theory.
The organization of retinofugal projections was studied in a cichlid fish by labelling small groups of retinal ganglion cell axons with either horseradish peroxidase or cobaltous lysine. Two major findings resulted from these experiments. First, optic tract axons show a greater degree of pathway diversity than was previously appreciated, and this pathway diversity is related to the target nuclei of groups of axons. The most striking example is the formation of the medial optic tract. Fibers that will become the medial optic tract move abruptly away from their neighbors, at about the level of the optic chiasm, and coalesce at the dorsomedial edge of the marginal optic tract. The medial optic tract projects to the thalamus, the dorsal pretectum, and the deep layer of the optic tectum. The axial optic tract is a group of fibers which segregates from the most medial portion of the marginal optic tract, at about the level of the optic chiasm. The axial tract stays medial to the marginal optic tract for a few hundred microns and then curves laterally to rejoin the marginal optic tract. At least some axial trat axons terminate in the suprachiasmatic nucleus. Within the marginal optic tract, retinal ganglion cell axons from a given retinal quadrant are always segregated into at least two groups. The smaller group projects to the superficial pretectal nucleus. The larger group projects to the superficial layer of the optic tectum.
This paper describes mechanisms of intracellular and intercellular adaptation that are due to spatial or temporal factors. The spatial mechanisms support self-regulating pattern formation that is capable of directing self-organization in a large class of systems, including examples of directed intercellular growth, transmitter production, and intracellular conductance changes. A balance between intracellular flows and counterflows causes adaptation. This balance can be shifted by environmental inputs. The decrease in Ca2+-modulated outward K+ conductance in certain molluscan nerve cells is a likely example. Examples wherein Ca2+ acts as a second messenger that shunts receptor sensitivity can also be discussed from this perspective.
The systems differ in basic ways from recent diffusion models. Chemical transducers driven by membrane-bound intracellular signals can establish long-range intercellular interactions that compensate for variable intercellular distances and are invariant under developmental size changes; diffusional signals do not. The intracellular adaptational mechanisms are formally analogous to intercellular mechanisms that include cellular properties which are omitted in recent reaction-diffusion models of pattern formation. The cellular models use these properties to compute size-invariant properties despite wide variations in their intercellular signals.
Mechanisms of temporal adaptation can be derived from the simplest laws of chemical transduction by using a correspondence principle. These mechanisms lead to such properties of intercellular signals as transient overshoot, antagonistic rebound, and an inverted U in sensitivity as intracellular signals or adaptation levels shift. Such effects are implicated in studies of behavioral, reinforcement, motor control, and cognitive coding.
The complementary distribution of the fibers from the olfactory bulb and the intracortical associational fibers to layers Ia and Ib, respectively, of the olfactory cortex has been examined in both adult and neonatal rats, using horseradish peroxidase (HRP) and ³ H‐leucine as double tracers in the same animal. The observations presented here confirm and extend the previous demonstration (Price, '73) that in the adult the two projections are essentially nonoverlapping throughout the olfactory cortex. Indeed, when the distribution of axons from the olfactory bulb (labeled by HRP inserted into a cut in the LOT) is compared on the same section with that of associational fibers (labeled by ³ H‐leucine injected into the cortex), the overlap between the two projections is limited to a zone only 5–10 μm in width in both the piriform cortex and olfactory tubercle.
In contrast, at P1 the two projections overlap throughout layer I, although the bulbar and associational fibers are slightly concentrated superficially and deeply in layer I, respectively. This overlap is especially prominent in the part of the anterior piriform cortex deep to the LOT. During the remainder of the first postnatal week, this overlap resolves and by P7 the segregation of the two sets of afferent fibers is nearly equivalent to that seen in the adult.
However, there are several instances in adults where the segregation of these afferents does not develop. First, a relatively small population of aberrant axons derived from the LOT may be traced from layer Ia into layer Ib and then back to layer Ia. Most of these axons are large in diameter and lack the boutonlike varicosities found on smaller axons in layer Ia. They are most prominent in areas where the cortex is highly curved. Second, in layer I of the nucleus of the lateral olfactory tract, bulbar and associational fibers are extensively intermingled. In this case also, the bulbar fibers are large in diameter with only a few boutonlike varicosities.
The developmental emergence of afferent segregation and its breakdown in cases where the fibers from the olfactory bulb do not form boutons suggest that an interaction between the two distinct sets of fibers and the dendritic field is responsible for the normal development of this segregation and that this interaction depends on the process of synaptogenesis.
This is a light and electron microscopic study of the retinotectal pathway: intact and after regeneration of the optic nerve. The spatiotemporal pattern of axonal outgrowth and termination was studied with the methods of proline autoradiography, horseradish peroxidase (HRP) labeling, and fiber degeneration.
The spatial order of optic fibers in the normal and regenerated pathways was assessed by labeling small groups intraretinally with HRP and then tracing them to the tectum. The labeled fibers occupied a greater fraction of the cross section of the regenerated than the normal optic tract. At the brachial bifurcation, roughly 20% of the regenerated fibers chose the incorrect brachium vs. less than 1% of the normals. In tectum, the regenerated optic fibers reestablished fascicles in stratum opticum, but they were less orderly than in the normals. The retinal origins of the fibers in the fascicles were established by labeling individual fascicles with HRP and then, following retrograde transport, finding labeled ganglion cells in whole-mounted retinas. Labeled cells were more widely scattered over the previously axotomized retinas than over the normal ones. A similar result was obtained when HRP was applied in the tectal synaptic layer. All of these results indicate that the pathway of the regenerated optic fibers is less well ordered than the intact pathway.
Both autoradiography and HRP showed that the regenerating optic fibers invaded the tectum from the rostral end, and advanced from rostral to caudal and from peripheral to central tectum, along a front roughly perpendicular to the tectal fascicles. Synapses of retinal origin were noted electron microscopically in the tectum at the same sites where autoradiography indicated that the fibers had arrived. No retinal terminals were seen where grain densities were at background levels. Fiber ingrowth and synaptogenesis apparently occurred simultaneously. The synapses were initially smaller and sparser than in normals, but were in the normal tectal strata and contacted the same classes of post synaptic elements as in normals.
In this review we consider a novel mechanism, "sibling neurite bias," which may explain aspects of the coordination of elongation, branching, and resorption among different neurites growing from the same neuronal cell body. In this model, growing neurites which incorporate structural precursors at higher rates would deplete the cellular pool of precursors available to their "sibling" neurites; neurites would compete for survival, but in addition they would bias each other's behavior during active growth. Evidence is reviewed that "sibling neurite bias" may contribute to the establishment and stabilization of specific neural connections. Specific examples examined include the loss of polyinnervation at the developing neuromuscular junction, contextual mapping in the retino-tectal system, and selective neurite growth patterns and synaptic connections in nerve tissue culture model systems.
The development of synaptic contacts between nerve cells and of the excitability of neuronal membranes are two important steps in the building of the nervous system. Hughes (1968a,b) was the first to state that during the normal course of development, connections are initially more diffuse than in the adult, i.e. the adult-type neuronal circuits derive not only from an increase in the total number of synaptic contacts, but also from the elimination of irrelevant connections. Indeed, this idea was not really new since at the turn of the century, Cajal (1911) had already described the presence of transient axonal projections in the central nervous system of mammals at early developmental stages.
The pathways of selected optic axons were traced in representative urodele, anuran, teleost, reptile, and avian species by filling the fibers with HRP or by tracing, at the light and electron microscopic (EM) level, the degeneration caused by focal or optic nerve lesions.
In all species it was shown that fibers retain retinotopic neighborhood relationships throughout their transit of the optic nerve. Additionally, inanurans, it was found that a subset of large diameter, myelinated fibers take up a random arrangement in the nerve. It is argued that retinotopic fiber organisation is a reflection fo contact guidance of axons during fiber outgrowth in the embryo and that this organisation could account for the arrival of fibers in orderly arrays at central nuclei during normal embryonic development.
We have reported previously that during optic nerve regeneration in Rana pipiens, axons are misrouted into the opposite nerve and retina. In the present investigation we have examined the time course of formation of these "misrouted" axons and their cells of origin. The right eye of 31 frogs was injected with 3H-proline at various times after right optic nerve crush. In every frog examined 2 weeks and later after nerve crush, the distribution of autoradiographic label indicated that axons from the right eye had grown into the left optic nerve at the chiasm. The amount of label increased from 2 weeks to reach a maximum at 6 weeks where the entire left nerve was filled with silver grains. At 5 to 6 weeks after crush, labeled axons were found within the ganglion cell fiber layer (GCFL) of the retina of the opposite eye for a maximum distance of 2.3 mm from the optic disc. In frogs examined at intervals later than 6 weeks after crush, the amount of label within the left eye and nerve progressively decreased, indicating a gradual disappearance of the misrouted axons. Studies using anterograde transport of horseradish peroxidase (HRP) after nerve injection confirmed these autoradiographic findings. The position of ganglion cells in the right eye whose axons were misrouted to the left eye was determined by retrograde transport of HRP. Five or 6 weeks after crushing the right optic nerve, the left eye was injected with HRP and labeled ganglion cells were found throughout the right eye retina. The largest percentage of labeled cells was found within the ventral half of the retina, particularly within the temporal quadrant, and nearly all of the labeled cells were found in more peripheral portions of the retina. Since few retino-retinal axons are found during normal development, the present results show that the factors guiding regenerating axons in the adult frog differ substantially from those present during development.
This chapter emphasizes recent studies with several types of co-cultures that appear to be particularly useful for analyses of neuronal specificity mechanisms in the central nervous system (CNS). Studies on the selective dorsal root ganglion (DRG) innervation of dorsal horn target regions in spinal cord explants, and on dorsal column nuclei in medulla explants, provide a valuable in vitro model system for analyzing some of the cellular mechanisms regulating the formation of specific neuronal connections in the mammalian CNS. These tissue culture models set limits to speculation on the minimum factors required to produce the complex gradients and/or neuronal cell recognition codes postulated to underlie selective growth of neurites throughout the CNS, and they may help to determine the properties of these gradients and codes. Systematic alterations of the physicochemical environment and the cellular constituents of the cocultures may lead to insights into critical factors required for the development of these specificity relationships. Cocultures of DRGs with critically positioned arrays of target and nontarget CNS explants may provide additional clues to mechanisms of preferential growth of neurites and establishment of specific connections. Similar experimental paradigms are also being applied to evaluate phenotypic specificity properties of retinal ganglion cells cocultured with tectal versus nontarget tissues.
The retina and optic nerve head have been examined by light and electron microscopy in adult Xenopus laevis after injury to optic nerve fibres. Intraorbital resection, transection or crush of the optic nerve all resulted in the appearance at the retina of a mass of actively growing axons which formed a ring around the intraretinal and adjacent choroidal portions of the optic nerve head. Formation of this heterotopic axon population was first noted at two weeks after nerve injury and fibres persisted for at least six months. The ectopic fibres were separated from the optic nerve head by astrocytes within the retina or by blood vessels and fibroblasts of the leptomeninges at extraretinal locations. In general, the orientation of the ectopic fibres was perpendicular to the fibres of the optic nerve. Bundles of axons were found between the ring of ectopic fibres and the pigment epithelial layer of the retina or among the blood sinuses of the choroid. Similar ectopic fibres were seen following transection of the optic nerve at the chiasm and after tectal ablation although the onset of these changes was slower than that seen after nerve resection. It is concluded that damage to visual pathways in the frog induces dramatic morphological alterations in the optic nerve and retina far proximal to the site of injury in this regenerating system.
In order to investigate the role of the different factors controlling the pathways and termination sites of growing axons, selected optic fibers were traced from the eye to the tectum in adult goldfish either by filling them with HRP, or by severing a group of fibers and tracing their degeneration in 2μm plastic sections stained with toluidine blue. Some fish received more than one lesion and others received both lesions and HRP applications. Two major rearrangements of the optic fibers were identified, one at the exit from the eye, the other within the optic tracts.
Near the eye the optic fibers appear to be guided by the conformation of the underlying tissue planes that they encounter. The most recently added fibers, from the peripheral retina, grow over the vitread surface of the older fibers toward the blood vessel in the center of the optic nerve head. Behind the eye the fibers follow this blood vessel until it leaves the side of the optic nerve, and the fibers from peripheral retina are left as a single group on the ventral edge of the optic nerve cross section. As a consequence of this pattern of fiber growth the fibers form an orderly temporal sequence in the optic nerve, with the oldest fibers from the central retina on one side of the nerve and the youngest from peripheral retina on the other. In addition, the fibers are ordered topographically at right angles to this central‐to‐peripheral axis, with fibers from ventral retina on each edge of the nerve, dorsal fibers in the center, and nasal and temporal fibers in between. This arrangement of the optic fibers continues with only a little loss of precision up to the optic tracts. A more radical fiber rearrangement, seemingly incompatibe with the fibers simply following tissue planes occurs within the optic tracts.
Each newly arriving set of fibers grows over the surface of the optic tracts so that the older fibers come to lie deepest in the tracts. This segregation of fibers of different ages ensures that the rearrangement is limited to each layer of fibers. The abrupt reorganization of the fibers occurs as the tracts split around the nucleus rotundus to form the brachia of the optic tracts. The fibers are then arranged with temporal fibers nearest the nucleus rotundus and nasal fibers on the opposite edges of the brachia. From this point the fibers grow out over the tectal surface to their termination sites with only minimal rearrangements. Therefore the optic fiber rearrangements show evidence of several different sorts of constraints acting on the fibers at separate points in the optic pathway, each contributing to the final orderly arrangement of the fibers on the optic tectum.
This chapter attempts to analyze the retinotectal system in a more empirical and open-ended fashion than that generally associated with past models. The traditional view of the problem is considered to be erroneous—that is, that no single simple explanation can account for all the observations because the task is to integrate a number of interactive processes into a comprehensive understanding. Such an integrative approach offers an alternative to the current wave of numerical modeling and thus skirts thorny theoretical issues that are associated with simulations of poorly described complex systems. Most hypotheses about how optic fibers form a retinotopic projection onto tectum have relied on a single dominant process to generate order. These processes largely fall into one of three categories. In the oldest category are those hypotheses that assume that individual retinal fibers or tectal cells are intrinsically identical with each other. In the latter, fibers were found to grow to abnormal tectal positions following removal of part of retina or tectum. The third category of explanation arose as an answer to the plasticity results. In particular, these hypotheses address the capacity of optic fibers to preserve retinotopography when a whole retina “compresses” onto a surgically formed half tectum or when a half retina expands across a whole tectum.
Die Ausbildung der sog. „funktioneilen Spezifität“ der Retinaanlage (im Sinne vonSperry undStone) wurde anTriturus vulgaris experimentell analysiert.
Die schon früher festgestellte Gesetzmäßigkeit, daß verschiedene Bezirke der Retinaanlage nach experimenteller Verlagerung (Achsendrehung) vor einem bestimmten Determinationszeitpunkt einelagegemäβe und nach diesem Zeitpunkt eineherkunftsgemäβe funktioneile Spezifität entwickeln, mußte gewisse Einschränkungen erfahren. — Die funktionelle Differenzierung der Retinaanlage geht wohl gemäß den beiden senkrecht aufeinanderstehenden Achsen voneinander unabhängig vor sich und auch die Zeitpunkte der Determination sind für die beiden Achsen verschieden, aber die Differenzierung längs einer (wenigstens der horizontalen) Achse liegender Teile der Retina ist voneinander abhängig.
Wird eine Augenanlage in dem Stadium, wenn einzelne Retinabezirke funktionell schon determiniert sind, andere dagegen noch nicht, operativ so umgebildet, daß einem aus schon determiniertem Material bestehenden Pol ein aus undeterminiertem Material aufgebauter Gegenpol gegenüberliegt, so entwickelt sich die funktionelle Spezifität dieses undeterminierten Teils nicht seiner Lage gemäß, sondern als Ergänzung (d. h. Gegenstück) zum schon determinierten Pol. — Innerhalb den Augenanlagen sind also „regulative Tendenzen“ nachweisbar, die darauf hinarbeiten, längs einer bestimmten Achse die funktionelle Spezifität nach einem einheitlichen Muster zu gestalten. Diese Regulation geht soweit, daß eine aus einer Hälfte der ursprünglichen Augenanlage umgeformte — nicht durch Regeneration ersetzte —, verkleinerte Augenanlage ein bezüglich funktioneller Spezifität vollkommenes Auge auszubilden vermag.
The order of production of retinal cells and the time when retinal cells become post-mitotic was studied in Rana pipiens embryos using 3H-thymidine autoradiography. Cell division stops first in the fundus of the retinal rudiment between embryonic stages 17 and 18 and gradually becomes restricted to the retinal margin. The ganglion cells in the fundus are among the first cells to become post-mitotic.
The specification of the central connections of ganglion cells was studied by rotating the eye primordium at embryonic stages 16–21. After metamorphosis, the visual projection from the rotated eye to the contralateral optic tectum was mapped electrophysiologically and compared with the normal retinotectal map. In all cases, the visual projection map was rotated through the same angle as was indicated by the position of the choroidal fissure. It appears that ganglion cell connections with the tectum were specified by stage 17. These results indicate that ganglion cell central connections are specified before the first ganglion cells become post-mitotic.
The specificity of the connections between the retina and the optic tectum has been studied in the chick by ablating between 15% and 75% of the optic cup (usually during the third day of incubation) and subsequently determining the distribution, within the tectum, of the synapses formed by the axons of the surviving ganglion cells. This was done towards the end of the incubation period, or shortly after hatching, either autoradiographically following the injection of a tritiated amino acid into the eye, or using a variant of the Nauta-Gygax method after sectioning the optic nerve. In every case in which the initial retinal lesion was placed after Stage 12/13 (i.e., late on the second day of incubation) the surviving ganglion cells could be shown to have formed synapses in only a limited region of the contralateral optic tectum; and as far as could be determined from an examination of the cell loss in the isthmo-optic nucleus (in which the centrifugal fibers to the retina have their origin) the remaining portion of the neural retina consistently projected only to the homotopic region of the tectum (i.e., the region to which it would normally have been expected to project). In several cases it was found that the axons had passed over a heterotopic region of the tectum in order to reach a more distant region in which they had formed synapses. After a lesion of the optic vesicle before Stage 11 the surviving ganglion cells appeared to innervate all parts of the tectum; since the earliest retinal ganglion cells are formed at Stage 11/12 it would seem that in the chick, as in Xenopus, there is a clear temporal co-incidence between the withdrawal of the first ganglion cells from the cell-cycle and the establishment of the topographic specification of the retino-tectal projection.
Retinogeniculate terminations have been studied by fiber degeneration and microelectrode mapping methods in normal cats and in Siamese cats in which the retinogeniculate pathway is congenitally abnormal. The normal representation of the visual field, including the monocular temporal crescent, has been determined. It has also been shown that there is a cellular discontinuity in lamina A which corresponds to the blind spot or optic disc. In normal cats four geniculate layers receive retinogeniculate terminals; two layers (A and C) receive contralateral and two layers (A1 and C1) receive ipsilateral afferents.
In Siamese cats laminae A and C are normal. Lamina A1 is broken up into four main cell segments. Two of these receive a normal input from the ipsilateral temporal hemiretina; two receive an abnormal projection from the contralateral temporal hemiretina. The abnormal projection originates primarily from a vertical strip of retina about 20°–25° in width that lies just temporal to the area centralis. Within this abnormal projection a normal retinotopic sequence is maintained but, since this projection goes to the contralateral instead of the ipsilateral lamina A1, the abnormal segments of lamina A1 receive a mirror-image of the normal representation.
Lamina C1 and the medial interlaminar nucleus receive an abnormal contralateral input from the temporal hemiretina similar to that found in lamina A1.
In adult goldfish the caudal half of the optic tectum was removed. In some animals the corresponding optic nerve was crushed as well. The animals were later used to map the retinotectal projection.
In fishes with the tectal lesion only, the displaced projection from the missing half-tectum was found to be partially restored over the residual rostral half-tectum, in appropriate retinotopic order. Parts of the residual tectum thus received input from two field positions.
In fishes with a tectal lesion and crush of the optic nerve, several animals showed compression of the projection of the entire visual field onto the residual half-tectum. In some animals reduplicated field positions were also observed.
The results are discussed in relation to the mechanism controlling selective fibre regeneration. It is concluded that a strict place-specificity does not exist along the rostrocaudal axis of the tectum and a mechanism of connection control involving pattern regulation is discussed.
The present experiments examine axonal sprouting of optic tract projections as a consequence of occipital cortex removal. Eyes were removed bilaterally in experimental rats 16 months following unilateral occipital cortex ablation. Seven animals survived this procedure. Controls included rats sacrificed 16 months after unilateral occipital cortex ablation, one week after unilateral occipital cortex destruction, and one week after bilateral or unilateral eye removal. Brains were serial-sectioned and stained by the Nauta-Gygax method for degenerating axons.
Sprouting occurred only at two loci, the caudal half of the ventral lateral geniculate nucleus, pars lateralis, and the caudal portion of lateral nucleus of the optic tract and subjacent medial quarter of pretectal nucleus. These loci have in common that they are regions of convergence in a major fashion of the two fiber systems, the occipitofugal and retinofugal projections on which experiments were done. However, sprouting did not occur in other similarly deafferented regions. Explanations for this specificity of sprouting are discussed.
Optic tract sprouting was observed only at paraterminal portions of the axon and not as collateral sprouts along its course.
A suggested relationship between axonal sprouting and functional plasticity is discussed.
In four species of freshwater fish, bass, carp, bluegill and goldfish, the topographical relations of the visual field with the contralateral optic tectum were investigated, using a small light as stimulus in the visual field and recording the electrical response of the tectum with a metal microelectrode. The results show a precisely organized visual projection onto the contralateral tectum in which the anterior visual field lies anteriorly on the tectum, the temporal field posteriorly, the dorsal field medio-dorsally, and the ventral field in the latero-ventral part of the tectum. The projection was found to be essentially linear and uniform with no indication of a specialized area in the visual field in those species investigated. Some receptive fields extended into the anterior binocular visual field.