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K F Hauser

Publications and source records attributed to K F Hauser.

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Granule cell development in the frog cerebellum during spontaneous and thyroxine-induced metamorphosis.

Granule cell maturation in the cerebellum of bullfrog tadpoles was studied during both spontaneous and thyroxine-induced metamorphosis by using electron microscopy and Golgi-impregnated preparations. The production of cerebellar microneurons, a majority of which are granule cell precursors, was quantitatively compared during spontaneous and thyroxine-induced metamorphosis by using stereological methods and biochemical measurements of DNA. Granule cell migration and differentiation appeared morphologically similar during spontaneous and thyroxine-induced metamorphosis. In both instances, granule cells migrated tangentially along the pial surface, migrated into the internal granular layer, developed dendritic arbors, and formed synaptic contacts with the processes of Golgi cells and with mossy fibers. These events are similar to developmental processes that have been described in detail in other animals. Quantitative stereological measurements demonstrated similar overall patterns of change during spontaneous and thyroxine-induced metamorphosis. Most notably, increases in the volume of the external granule layer correlated with increases in the relative and total amounts of DNA. However, measurements of total DNA were consistently reduced during the period of accelerated change that occurs in thyroxine-induced metamorphosis, although external granular layer volume was greater in these tadpoles after 2 and 3 weeks of thyroxine treatment than in spontaneously metamorphosing tadpoles. While granule cell development in the frog is largely dependent on thyroid hormone, differences between thyroid-hormone-induced and spontaneously metamorphosing tadpoles suggest that normal patterns of cerebellar development are also dependent on events that occur in premetamorphic tadpoles in the absence of thyroid hormone.

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Stellate cell development in the frog cerebellum during spontaneous and thyroxine-induced metamorphosis.

Stellate cell development was studied in the bullfrog cerebellum during spontaneous and thyroxine-induced metamorphosis using the Golgi-Kopsch method and electron microscopy. Cells that possessed axosomatic synapses and resembled stellate cells were present even in the incipient molecular layer of the cerebellum in the premetamorphic tadpole. These cells may have originated from the early, transient wave of external granule cells that have been reported in the cerebellum of premetamorphic tadpoles in the first 6 months of development, and may constitute the variant population of stellate cells that are present later during development or the degenerating cells that have been observed during metamorphosis as scattered dying cells in the molecular layer. Typical stellate cells, whose development resembled the genesis and differentiation of stellate cells in birds and mammals, were initially observed at the outer border of the molecular layer that is adjacent to the external granular layer during the onset of metamorphosis. These stellate cells were bipolar with processes extending in a plane perpendicular to elongating parallel fibers, and with progressive development, became multipolar with dendrites oriented in various directions with respect to the pia. Stellate cell axons innervate the dendrites and somata of Purkinje cells and other stellate cells, and can be categorized into two types: (1) axons with extensive branching near the soma of origin, and (2) long axons with few branches that occasionally terminate in the Purkinje cell layer. Atypical neurons that did not resemble typical stellate cells were also present in the molecular layer; these might be classified as a stellate cell variant. The generation and differentiation of stellate cells can be induced 1 to 2 years prematurely by administering thyroid hormone to premetamorphic tadpoles. Like most events of cerebellar histogenesis in the frog, stellate cell development also appears to be largely a thyroid-dependent phenomenon.

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Purkinje cell maturation in the frog cerebellum during thyroxine-induced metamorphosis.

Purkinje cell maturation during thyroxine-induced metamorphosis in premetamorphic bullfrog tadpoles was studied using electron microscopy and Golgi (silver-impregnated) preparations. Cerebella from tadpoles were examined following 1, 2, or 3 weeks of thyroxine treatment. Particular attention was paid to possible differences between the two populations of Purkinje cells previously described, i.e. (i) the smaller population located in the dorsal part of the cerebellum, where the Purkinje cells show dendritic arborization long before the appearance of the external granular layer, and (ii) the larger population located in the middle and ventral regions of the cerebellum, where the Purkinje cells begin to undergo maturation during metamorphosis when the external granular layer is established. Following thyroxine treatment, both populations of Purkinje cells showed rapid maturational change. In the mature (dorsal) group, dendritic growth resumed in the presence of an external granular layer increasing the complexity of their dendritic arbors. Moreover, climbing fiber synapses translocated from contacts on the soma to the thorns of growing dendrites, and somatic processes often disappeared. The immature (ventral) group showed dramatic differentiation of the perikaryon including polarization of cytoplasm with subsequent dendritic outgrowth and formation of somatic processes in the presence of climbing fibers. Stellate cell contacts appeared on the smooth portion of the soma of many Purkinje cells. Dendritic growth during thyroxine-induced metamorphosis was characterized by growth (elongation) with minimal branching, which is initially observed during spontaneous metamorphosis. Typically, these growing dendrites ended in growth cones, some with one or several filopodia. Developing Purkinje cell dendritic spines formed synapses with parallel fibers. The present study has provided an example of the dramatic nature of thyroxine's action in inducing the complex series of detailed maturational changes in the cerebellum 1-2 yr ahead of schedule. In addition, the results show that thyroxine-induced Purkinje cell maturation is more rapid and synchronous than that seen during spontaneous metamorphosis. It is concluded that Purkinje cell maturation during metamorphosis is largely dependent on thyroid hormone.

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Effects of thyroidectomy and season on the external granular layer of the cerebellum in metamorphosing bullfrog tadpoles (Rana catesbeiana).

Transient formation of the cerebellar external granular layer (EGL) occurs during metamorphosis in frog tadpoles and is dependent on thyroid hormone. Late prometamorphic bullfrog tadpoles at similar stages of development were thyroidectomized and then killed after 1 month and 2 months during the fall and winter. The cerebellum was studied by qualitative and quantitative light microscopy. Thyroidectomy resulted in an inhibition of external metamorphic changes such as hind limb growth. Examination of the cerebellum after thyroidectomy showed the EGL greatly decreased in thickness after 1 month and in some cases was altogether absent after 2 months. Because the disappearance of EGL cells was a result of their inward migration into the IGL, we conclude that thyroid hormone was not necessary for granule cell migration. In addition, metamorphic change normally occurs in the late spring and summer in bullfrog tadpoles, and is inhibited during the fall and winter (metamorphic stasis). During the winter, the volume of the EGL was significantly less compared with tadpoles undergoing active metamorphosis. Although lowered temperature appears to contribute to the large decline in EGL thickness, significant seasonal differences in the EGL volume ratio were still observed in tadpoles maintained under conditions of constant temperature and light. Thyroxine administered to thyroidectomized tadpoles during the winter increased the thickness of the EGL. Therefore, the seasonal decline in the EGL thickness reflects a decrease in thyroid hormone activity, which in turn appears controlled by both internal (hypothalamic) and environmental (e.g., temperature) factors.

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Ultrastructural studies on the ventricular surface of the frog cerebellum.

Ultrastructural studies of the ventricular surface of the frog cerebellum showed regional differences. In the midline region of the adult cerebellum was found a band of profusely ciliated squamous ependymal cells. In the rest of the cerebellum the ependymal cells were columnar and each had a single cilium. In the cerebellum of the premetamorphic tadpole, the squamous ependymal cells of the midline region also were monociliated. During metamorphosis they gradually became multiciliated. Additionally, supraependymal cells and synaptic elements were present on the ventricular surface of the cerebellum of adult frogs as well as in late metamorphic tadpoles. In contrast, supraependymal cells were rarely observed in premetamorphic tadpoles, and it was concluded that the supraependymal system develops during metamorphosis. It is postulated that the band of cilia may be associated with the circulation of cerebrospinal fluid, and supraependymal synaptic elements function in neuroendocrine regulation.

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Ultrastructural studies on Purkinje cell maturation in the cerebellum of the frog tadpole during spontaneous and thyroxine-induced metamorphosis.

The maturation of Purkinje cells in the cerebella of both thyroxine (T4)-induced and normally metamorphosing tadpoles was studied by transmission electron microscopy, with particular reference to the perikaryal changes. During the latter part of the prometamorphic phase, many Purkinje cells showed hypertrophied apical cones filled with mitochondria, Golgi elements and rosettes of ribosomes. In early metamorphic climax, the perikaryal cytoplasm displayed stratification, with an inner zone of perinuclear Nissl bodies and an outer region of neurotubules. At the onset of metamorphic climax, there was an abrupt appearance of numerous somatic processes, as well as climbing fiber boutons which synapsed with them on some cells. However, many Purkinje cells did not display somatic processes. Stellate cell synapses also were seen in considerable numbers. As metamorphic climax progressed to completion, the somatic processes steadily grew scarce with a concomitant increase in climbing fiber synapses on the major dendrites. Glial ensheathment of the Purkinje cell soma was also rapidly accomplished during metamorphic climax. In addition, premetamorphic bullfrog tadpoles were induced to metamorphose prematurely following treatment with T4 and then compared to normally metamorphosing tadpoles. Following 3 weeks of T4 treatment, large numbers of Purkinje cells displayed somatic processes. These processes were observed to be postsynaptic to climbing fibers and similar to those seen normally. Additionally, Purkinje cell hypertrophied apical cones were observed in treated tadpoles. These observations indicate that some aspects of Purkinje cell maturation during metamorphosis, especially the interaction of climbing fibers and somatic contacts, are T4-dependent. In both normal and induced metamorphosis, changes in frog Purkinje cells thus proceed at a tempo comparable to that of such gross morphological transformation as hindlimb growth.

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