Search PubMed⌕ Search

Biomedical subjects

L Schweitzer

Publications and source records attributed to L Schweitzer.

At least 55 records · Page 3Linked to original sources

Morphometric analysis of developing neuronal geometry in the dorsal cochlear nucleus of the hamster.

Since the shape of a cell's dendritic field and the distribution of its input determine the information that a cell receives and transmits, it is important to ascertain how the spatial relations between axonal arbors and dendritic fields develop. This study investigates the development of the dendritic fields of fusiform cells in the dorsal cochlear nucleus. Golgi-impregnated cells from postnatal day 10, 15, 25, 45 and 60+ hamsters were reconstructed. The computerized morphometric system used analyzed cells in the plane of section and also allowed rotation to and analysis in other specified planes, such as that parallel to the terminal arbors of the cochlear nerve fibers. The results suggest that the apical dendritic fields are oriented parallel to the axis of cochleotopic organization and that this orientation develops gradually after birth. Dendritic growth is the result of addition of new dendritic branches. The angles between branches also change and were analyzed by viewing the dendritic fields in different planes. This revealed that some preferential expansion of the apical dendritic field in the plane parallel to the cochlear projection planes is the result of increased angles between branches in that plane. Thus, dendritic growth via the addition of branches and the 'fanning-out' of existing branches underlie the development of oriented dendritic fields.

Animals↗

Details of the central projections of the cochlear nerve in the hamster revealed by the fluorescent tracer DiI.

A new fluorescent tracer, DiI, may be used postmortem in perfused animals making placement in small structures such as the cochlea much less difficult. We have mapped cochlear nerve terminations in the cochlear nucleus with DiI and, using three-dimensional reconstructions, have demonstrated the topography and geometry of the cochlear input. By placing DiI in two regions of the cochlea, we have demonstrated that terminations from the cochlea form stacked sheets of inputs. If enough closely situated ganglion cells were labeled in the cochlea, a well-delineated stripe of label could be found in each section of the cochlear nucleus up to the superficial granule cell region. Here a small extension of label, separate from the stripe may represent the medial olivocochlear axons. When fewer axons were labelled in the cochlear nerve, the sheets were absent and discontinuous patches of label were found. These patches apposed rostrocaudally to form bands of label that run orthogonal to the tonotopic organization.

Animals↗

Differentiation of apical, basal and mixed dendrites of fusiform cells in the cochlear nucleus.

Many studies suggest that the details of morphogenesis (e.g. the length and number of dendrites) are determined by factors extrinsic to the cell, while the basic form of the neuron (e.g. the shape of the soma and the placement of the primary dendritic trunks) is determined by intrinsic factors. The following study describes the development of the dendrites of fusiform cells in the dorsal cochlear nucleus of the hamster using Golgi-stained brains from hamsters of various ages. Two basic types of dendrites are described--apical and basal--which emanate from opposite ends of the cell body and differ in their morphology. A third type of dendrite that exits the cell laterally can create a deflection in the perimeter of the cell body altering its shape. The morphology of these dendrites is described and compared to the apical and basal dendrites. Segments of laterally extending dendrites that are near apical dendrites are qualitatively and quantitatively identical to apical dendrites (that is they branch frequently and are spine-laden) and the converse is true of the segments near basal dendrites. The results suggest that during development, whether a dendritic will be apical-like or basal-like is determined by the location of its distal segment. Thus, extrinsic factors influence the overall form of these neurons.

Animals↗

Dendritic development of Purkinje and granule cells in the cerebellar cortex of rats treated postnatally with alpha-difluoromethylornithine.

Postnatal administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), is known to curtail replication of granule cells in the cerebellum of the rat, but its effects on post-proliferative neurons is unknown. This Golgi study assessed the influence of daily postnatal injections of DFMO on dendritic development of the Purkinje and granule cells. Although the overall appearance of the Purkinje cells was normal, DFMO affected morphogenesis by causing: 1) a reduction in somatic growth, 2) an elongation of the primary dendrite, 3) a lengthening of the distance between the soma and the pial surface, 4) a reduction in the number of tertiary dendrites, and 5) a disruption of the distribution of the tertiary branches. Many of these effects of DFMO may be mediated via the reduction of granule cells rather than representing a direct effect on dendritogenesis. In addition to reducing the number of granule cells, the distribution and morphology of these cells in the DFMO-treated rats were severely affected. Many granule cells did not complete their migration and remained trapped in the molecular layer, and many of those trapped had greatly elongated dendrites that extended into the internal granule cell layer. These results suggest that ornithine decarboxylase is involved in the postproliferative processes of neuronal migration and differentiation.

Animals↗

Ontogenetic changes in laminar distribution of ornithine decarboxylase during development of cerebellar cortex: autoradiographic localization with [3H]alpha-difluoromethylornithine.

Ornithine decarboxylase is the first enzyme in the biosynthesis of the polyamines, which control macromolecule synthesis during cellular development. Polyamines appear to play a critical role in the development of the rat cerebellar cortex, since postnatal treatment with the specific irreversible ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, arrests cell division and migration in this region. To determine whether the distribution of ornithine decarboxylase within the developing cerebellar cortex correlates with specific maturational events, [3H]alpha-difluoromethylornithine, a specific marker for ornithine decarboxylase activity, was localized autoradiographically in 3-13-day-old rats. The density of autoradiographic grains within the cerebellar cortex as a whole paralleled the postnatal rise and fall of biochemically determined ornithine decarboxylase activity. Superimposed on this pattern was a selective laminar distribution of label which indicated specific association of ornithine decarboxylase with cell replication, as shown by preferential labeling of the superficial (mitotic) zone of the external granule cell layer. In addition, ornithine decarboxylase activity was temporally associated with regions in which post-mitotic cells were undergoing migration, axonogenesis and dendritic arborization, as shown by the patterns obtained in deeper layers. In contrast, there was no evidence for an association between ornithine decarboxylase activity and synaptogenesis, gliogenesis or myelination. These results, in combination with previous biochemical and morphological data, support the view that the ornithine decarboxylase/polyamine system plays an important role in both mitotic and post-mitotic events within the nervous system.

Animals↗

Impaired morphological development of the dorsal cochlear nucleus in hamsters treated postnatally with alpha-difluoromethylornithine.

The dorsal cochlear nucleus is a highly organized nucleus in the auditory system in which the ramifications of depletion of specific cell types during development can be studied. Granule cells, small interneurons that are located in all layers of the DCN in the adult hamster, proliferate postnatally and are, therefore, potentially vulnerable to anti-mitotic agents that are administered after birth. The present experiments describe the effects of alpha-difluoromethylornithine, a drug that inhibits proliferation of cerebellar granule cells, on the granule cells in the dorsal cochlear nucleus. As in the cerebellum, the density of granule cells in the dorsal cochlear nucleus is reduced after alpha-difluoromethylornithine treatment. In hamsters treated with alpha-difluoromethylornithine (200 or 500 mg/kg subcutaneously (s.c.), twice daily on postnatal days 4-14), the numerical density of granule cells was reduced in the superficial dorsal cochlear nucleus at 15 days; by 40 days this effect was also apparent in the deep layer, suggesting that cells located superficially that would have migrated into the deep dorsal cochlear nucleus had either failed to develop or did not arrive at their final location. This evidence suggests that the cells normally migrate down from the superficial proliferative zone into the deeper layers. In the drug-treated animals, a layer of mixed granule cells and fusiform cells was thinner than in controls probably due to the reduction in interspersed granule cells since the number of fusiform cells was unaffected. There was also a dose-dependent effect on cell growth; fusiform cells were affected at both doses, while giant cells were only affected at the highest dose. Granule cells form a major input to the fusiform cells and their depletion may account for some of the effects on fusiform cell growth. There could also be additional direct actions of alpha-difluoromethylornithine on this population.

Age Factors↗

Development of brainstem auditory evoked responses in the hamster.

The hamster is relatively immature at birth compared with other mammalian species. Because of the amount of maturation that occurs postnatally, the development of the peripheral auditory system of the hamster has generated a great deal of interest. However, indices of the developing functional capabilities of the central auditory system of the hamster are lacking. The following study investigated the ontogeny of brainstem auditory evoked responses (BAERs) to clicks in young hamsters. The general maturational trends noted for other species were found for the hamster. The major peaks of the BAER decrease in latency at the same time relative to birth and at the same rate in the hamster as in the cat and rat. Some maturational events such as the onset of a recordable BAER, appearance of the late peaks and increase in amplitude of the late peaks occur later, relative to birth, in the hamster than in the other species. Development delays in the hamster make it an attractive model for studying postnatal development of the central auditory system.

Aging↗

Immunoreactivity to calcitonin gene-related peptide in the superior olivary complex and cochlea of cat and rat.

In both cat and rat, the cells of origin, axons, and terminals of the lateral olivocochlear system exhibit immunoreactivity to antisera to calcitonin gene-related peptide (CGRP). In the cat, immunoreactive neurons in the brainstem are located in the hilus of the lateral superior olivary nucleus and around its margins. In the rat, immunoreactive neurons are located within the lateral superior olivary nucleus proper. In both species, immunoreactivity in the cochlear duct is limited to the region beneath the inner hair cells. Immunoreactive axons in the cochlear nucleus could not be traced to their source but may arise as collaterals of the lateral olivocochlear system. No other components of the brainstem auditory system react to any extent with the antisera.

Animals↗

[New echocardiographic para-apical technic for determining the size and thickness of the wall of the right ventricle in probands and patients with dilated cardiomyopathy].

To evaluate the right ventricular size and free wall thickness a new echocardiographic para-apical technique was developed. All cases were examined from the para-apical window in the extreme left lateral decubitus position, on a special mattress that allowed us to investigate the total apical region. The para-apical transducer position makes it possible to cut the right ventricle cross-sectionally in serial bread-loafing fashion from the apex to the base, like the left ventricle. In this way, using the M-mode technique, either diameters and/or right ventricular free wall thickness as well as shortening fraction could be estimated. To estimate the usefulness of the para-apical technique, a study was performed in 50 normal subjects as well as in 16 patients with dilated cardiomyopathy. In all patients, standard views and the new para-apical view were performed. In five cases, contrast echocardiography of the heart was performed to verify the right-heart anatomy. In five patients, computer-tomography of the heart was performed to see the position of the right-heart chambers in the chest and to evaluate the new para-apical ultrasound window. The standard values for the right ventricle in the control group were (in mean values): diastolic diameter, 28.61 +/- 3.19 mm; systolic diameter, 19.10 +/- 2.40 mm; free wall thickness, 4.46 +/- 1.06 mm and shortening fraction, 32.42% +/- 4.02%. The examined parameters in patients with dilated cardiomyopathy were: diastolic diameter, mean value 38.63 +/- 5.80 mm; systolic diameter, mean value 32.48 +/- 4.96 mm; free wall thickness, mean value 8.70 +/- 1.05 mm and shortening fraction, mean value 15.96 +/- 4.02%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Identification of polyamines in the cochlea of the rat and their potential role in hearing.

The occurrence of reversible hearing loss in patients treated with the polyamine biosynthesis inhibitor, alpha-difluoromethylornithine (DFMO), led to the hypothesis that this functional hearing deficit might be due to polyamine depletion in the cochlea. To test this hypothesis the polyamine content (putrescine, spermidine and spermine) of the cochleas of normal rats was measured and compared to that of DFMO-treated rats. For the first time, it was demonstrated that in the cochleas of normal rats there were substantial amounts of spermidine and spermine but no detectable putrescine. There was also no measurable ornithine decarboxylase. The DFMO treatments employed in this study were not effective, however, in depleting the cochlear polyamines to levels generally considered critical for disrupting polyamine-dependent processes in other systems. Thus, it is not surprising that auditory thresholds, which were evaluated using brainstem evoked potentials, remained unaltered in the DFMO-treated rats. Demonstration of a role for polyamines in hearing awaits further investigation with the use of more potent inhibitors or other model systems for hearing.

Animals↗

Differentiation of the giant and fusiform cells in the dorsal cochlear nucleus of the hamster.

Two categories of large neurons--fusiform cells and giant cells--can be distinguished in the dorsal cochlear nucleus of the hamster. In the adult, these neurons are located in separate laminae in the nucleus and have distinct dendritic morphology. However, the two cell types are not distinguishable in the newborn hamster. At birth the large cells in the dorsal cochlear nucleus are clustered into one group and are alike morphologically. On postnatal day 5, laminae are still not apparent, but the neurons have begun to acquire their adult shapes. By day 15 laminae have formed, and the cells appear mature with the one exception that the apical dendrites of the fusiform cells have not acquired the spines which will cover their surface in the adult. The appearance of laminae coincides with the growth of axons and dendrites into a interstitial zone between the layers of cell bodies. Dendritic growth occurs during the time of axonal ingrowth and establishment of contacts between the axons and dendrites. The growth of the apical dendrites of fusiform cells, which are not contacted by these fibers, lags behind. These results demonstrate that afferent ingrowth and the differentiation of dendrites in the dorsal cochlear nucleus are temporally related. The synchronous development may serve to ensure a specific synaptic arrangement between the axons and their target dendrites.

Animals↗

Development of oriented dendritic fields in the dorsal cochlear nucleus of the hamster.

The shapes of the apical and basal dendritic fields of the fusiform cells in the dorsal cochlear nucleus of the hamster were analyzed quantitatively. Measurements of the cross-sectional areas of the dendritic fields in planes parallel and perpendicular to planes occupied by the cochlear nerve axons revealed that the apical dendrites have a preferential orientation with respect to the cochlear planes. No consistent orientation of the basal dendrites was apparent. The orientation of the apical dendrites is not present in the neonatal hamster; rather, it develops gradually and is not fully established until after postnatal day 25. Since the cochlear fibers grow into the dorsal cochlear nucleus, establish contacts and become functional before day 25, the presence of the cochlear input might be a prerequisite for the development of oriented dendritic trees. In adult hamsters that have had their cochlear input eliminated during infancy, the apical dendritic trees of the fusiform cells are not oriented normally. The results suggest that the presence of the afferent input is necessary for the differential growth that leads to the development of oriented dendritic trees.

Animals↗

Impaired development of cerebellar cortex in rats treated postnatally with alpha-difluoromethylornithine.

alpha-Difluoromethylornithine specifically and irreversibly inhibits the enzyme ornithine decarboxylase. Ornithine decarboxylase catalyses the initial step in the synthesis of polyamines, which are thought to play an essential role in growth and development of mammalian tissues. The current study examined the effects of alpha-difluoromethylornithine on the ontogenic development of the rat cerebellar cortex. Animals injected daily with alpha-difluoromethylornithine on postnatal days 1-21 suffered a deficit in the number of granule cells and many of the remaining granule cells became trapped in the molecular layer during migration. Purkinje cells were also scattered throughout the molecular layer and their mean diameter was 38% smaller than in controls. In general, the cerebellar cortex of alpha-difluoromethylornithine-treated rats failed to progress much beyond the stage of development reached in control rats during the first postnatal week. These effects of alpha-difluoromethylornithine were already clearly visible at 10-15 days of age. The final size of the cerebellum as a whole and of individual folia was markedly subnormal. These data indicate that polyamines play an obligatory role in cerebellar neurogenesis and histogenesis.

Animals↗

Development of the cochlear innervation of the dorsal cochlear nucleus of the hamster.

The development of cochlear fibers and terminals in the dorsal cochlear nucleus of the hamster was studied with light and electron microscopic techniques. Like the dorsal cochlear nucleus of most other mammals, the dorsal cochlear nucleus of the adult hamster is a laminated structure. Three distinct layers can be identified in cresyl-violet-stained sections: the molecular layer, the fusiform cell layer, and the deep layer. The deep layer consists of a superficial zone, free of large cell bodies, and a deep zone which contains the somas of giant cells. Horseradish peroxidase and degeneration studies reveal that the cochlear fibers ramify throughout the deep and fusiform cell layers of the adult hamster but do not enter the molecular layer. In the electron microscope, three types of terminals that contact the fusiform and the giant cells can be distinguished. Only one type of terminal (type LR) degenerates after cochlear ablation and is, therefore, thought to be of cochlear origin. Type LR terminals are found throughout the deep and fusiform cell layers and contact the somas of giant and fusiform cells, as well as their intermingled dendrites in the deep layer. In Golgi-impregnated material, cochlear fibers are not found in the dorsal cochlear nucleus of the neonatal hamster, although they have entered the ventral cochlear nucleus. Ingrowth of cochlear fibers into the dorsal cochlear nucleus occurs over the first postnatal week and one-half. A spatial gradient is evident during the ingrowth of the fibers in that they invade the dorsomedial parts of the dorsal cochlear nucleus before they invade the ventrolateral parts. In all parts of the nucleus, the fibers enter the deepest layer and grow progressively more superficially. In the electron microscope, the first appearance of type LR terminals at each depth lags behind the ingrowth of the fibers by about two days. In hamsters, fibers from the basal turns of the cochlea terminate in the dorsomedial dorsal cochlear nucleus, while fibers from the apical turns terminate in the ventrolateral dorsal cochlear nucleus (DCN). The dorsomedial to ventrolateral gradient in the ingrowth of the cochlear fibers into the DCN indicates that the fibers from the basal turn are the first to arrive. Several components of the mammalian cochlea have been shown to mature at the base of the cochlea before they mature at the apex. The present study suggests that maturation gradients in the cochlear nucleus parallel those observed in the cochlea.

Animals↗

Acquisition and extended retention of a conditioned taste aversion in preweanling rats.

The time course of memory decay for infant rats may shed light on the processes responsible for infantile amnesia. A taste aversion conditioning procedure appropriate for both neonatal and adult rats was employed in four experiments to investigate the ontogeny of extended retention. In Experiment 1, rats trained at 1, 10, 20, or 60 days of age were tested for retention of the taste aversion 25 days later. At testing, only those rats conditioned when 20 or 60 days old demonstrated significant taste aversions. Experiments 2 and 3 established that rats 14-15 days old and older were able to retain significant taste aversions following a 25-day retention interval. Younger rats did, however, acquire and retain the aversion for several days and showed a gradual retention loss over progressively longer retention intervals (Experiment 4). These findings suggest that preweanling rats demonstrate initial consolidation, storage, and retrieval of conditioned taste aversions. It is only after this initial period that retention deficits become evident.

Aging↗

Evidence of right cerebral hemisphere dysfunction in schizophrenic patients with left hemisphere overactivation.

A number of laterality studies have used initial lateral eye movements as a measure of unbalanced frontal hemisphere activity. Several of these studies have demonstrated that schizophrenics look to their right more often than normals or depressives when thinking about spatial and/or emotional material. This increase in right gaze responses has been taken to represent increased left hemisphere responsiveness for spatial and emotional material. Thus, it was predicted that schizophrenics would be more receptive to spatial material and would detect rapidly appearing spatial stimuli presented to their left hemisphere more accurately than in their right hemisphere. Further, it was expected that schizophrenics would perform better than controls when identifying rapidly presented shapes in the left hemisphere. Using visual half-field presentation of verbal and spatial material, the experimental prediction of increased left hemisphere accuracy for shape detection within the schizophrenic group was corroborated. However, there was an unanticipated and significant right hemisphere deficit for spatial identification between the schizophrenic group and the normal controls. This finding suggests that schizophrenics may have a primary deficit in their right hemisphere, which affects visuospatial processing. It is suggested that the apparent left hemisphere increase in activity for spatial material reported by Gur and Schweitzer may thus be a compensatory mechanism for a primary failure of the schizophrenic's right hemisphere to maintain normal attention and vigilance.

Discrimination Learning↗