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L Schweitzer

Publications and source records attributed to L Schweitzer.

At least 37 records · Page 2Linked to original sources

Structure and function of gustatory neurons in the nucleus of the solitary tract: II. Relationships between neuronal morphology and physiology.

This study employed intracellular recording and labeling techniques to examine potential relationships between the physiology and morphology of brainstem gustatory neurons. When we considered the neuronal response to the four "prototypic" tastants, we were able to demonstrate a positive correlation between breadth of responsiveness and the number of dendritic branch points. An analysis of the response to eight tastants also revealed an association between dendritic spine density and the breadth of responsiveness, with more narrowly tuned neurons exhibiting more spines. Interestingly, a neuron's "best response" was a relatively poor predictor of neuronal morphology. When we focused on those neurons that responded to only one tastant, however, a number of potentially important relationships became apparent. We found that the cells that only responded to quinine were smaller than the neurons that only responded to NaCl, HCl, or sucrose. The HCl-only neurons, however, were more widespread in the rostrocaudal dimension that the neurons that only responded to NaCl. A number of additional structure-function relationships were identified when we examined the neuronal response to selected tastants. We found that neurons that responded to sucrose but not quinine, as well as neurons that responded to quinine but not sucrose, were more widespread in the mediolateral dimension than neurons that responded to both sucrose and quinine. We also discovered that the neurons that responded to NaCl, but not to NH4Cl or KCl, were larger than neurons that responded to all three salts. We believe that these results support the hypothesis that there are relationships between the structure and function of gustatory neurons in the nucleus of the solitary tract, with the data highlighting the importance of three themes: 1) the relationship between dendritic specializations and tuning, 2) the relationship between dendritic arbor orientation and response properties, and 3) the potential importance of stimulus-specific neurons.

Animals↗

Anatomical correlates of the passive properties underlying the developmental shift in the frequency map of the mammalian cochlea.

As the cochlea develops, the cells in the basal cochlea become sensitive to progressively higher frequencies. To identify features of cochlear morphology that may underlie the place code shift, measurements of infant and adult gerbil cochleas were made at both the light and electron microscopic levels. The measurements included areas of the cochlear duct, basilar membrane, and organ of Corti, height and width of the basilar membrane, thickness of the tympanic cover layer, thickness of the upper and lower basilar membrane fiber bands, and optical density of the basilar membrane. The results indicated that basilar membrane dimensions do not change as the place code shifts and that regions that code for the roughly the same frequency (e.g., approximately 11.2 kHz) at different ages can have basilar membranes of very different dimensions. In contrast, the size of the organ of Corti and the thickness of fiber bands inside the basilar membrane do change in ways consistent with the shift in the frequency map.

Acoustic Stimulation↗

A therapeutic preschool for abused children: the KEEPSAFE Project. Kempe Early Education Project Serving Abused Families.

Twenty-four children attended a therapeutic preschool for physically and sexually abused children, the Kempe Early Education Project Serving Abused Families (KEEPSAFE), over a 3-year period from 1985-1988. The program provided early education and therapy for abused children so that they could improve developmentally, socially, and emotionally, with the aim that the children would be suitable to enter the public education system. The therapeutic preschool was combined with a home visitation program for the child's parents or primary caretaker, focusing on improving the quality of interaction between the adult and child. The majority of children made developmental gains at a faster rate than would normally be expected as measured by the McCarthy Scales of Children's Abilities and the Peabody Picture Vocabulary Test. Although all 24 children were thought at onset of intervention to be unable to participate in a public school setting, after 12 months in the program over 79% were staffed into the public school system eight (33.3%) into a regular classroom. Three others (12.5%) needed residential care, and two were too young to enter public school. Even though a therapeutic preschool is expensive in terms of the high staff to child ratio needed, it is likely to be beneficial in improving the developmental skills of abused children.

Child Abuse↗

Cell types in the rostral nucleus of the solitary tract.

The rostral subdivision of the nucleus of the solitary tract (rNST) is not laminated or otherwise organized into clearly segregated cell types. Although a variety of experimental approaches have yielded a wealth of information, the definition of cell types in this nucleus has been difficult, as reflected in the sometimes contradictory literature on morphological cell typing. The present review discusses how rNST neurons have been classified in the past and adds to the evidence that distinct neuron types exist in this nucleus. Consistencies in the literature, as well as inconsistencies among studies, are discussed. Furthermore, we have included a summary of our own results that help provide additional data relevant to cell typing. The definition of cell types in other central nervous system nuclei has helped our understanding of the organization of these nuclei and our understanding of the relationships between the morphology and function of neurons. It is hoped that this synthesis of the extant literature will facilitate the many ongoing efforts to correlate neuronal morphology and physiology in the gustatory system.

Animals↗

Longitudinal and radial differences in the subsurface cisternal system in the gerbil cochlea.

Many features of cochlear anatomy vary systematically radially and longitudinally within the organ of Corti. There is limited evidence that along the longitudinal axis of the cochlea the thickness of the subsurface cisternal system in the outer hair cells (OHCs) changes. Similarly a radial gradient may exist. The thickness of the subsurface cisternal system in OHCs was measured in gerbils to determine if there are differences between the three rows of OHCs and in OHCs in different locations along the length of the organ of Corti. The results suggest that there is a longitudinal as well as a radial gradient of subsurface cisternal system thickness. These gradients are the inverse to those for efferent innervation of OHCs. It is possible that these differences may contribute to the increased susceptibility to trauma and ototoxic compounds characteristic of the innermost and basalmost OHCs.

Analysis of Variance↗

The development of glycine-like immunoreactivity in the dorsal cochlear nucleus.

Both anatomical and physiological lines of evidence suggest that inhibitory influences are active early in the development of the dorsal cochlear nucleus (DCN). Data from physiological/pharmacological studies suggest that in the adult these inhibitory influences may be mediated at least in part by the neurotransmitter glycine. Using a polyclonal antibody to examine the development of glycine in the DCN, we have observed that glycine-like immunoreactive cell bodies and punctate label are present in the DCN by the day of birth in the hamster and in the kitten at least 10 days prior to birth. In contrast to the development of immunoreactivity for glutamic acid decarboxylase (GAD) (Schweitzer et al., 1993), glycine-like immunoreactivity shows a homogeneous distribution throughout the DCN from the day of birth through adulthood. In addition, glycine immunoreactivity is present earlier than GAD-immunoreactivity and is present well before these brain structures become responsive to air-borne sounds. Thus, glycine is present in the very young animal and may mediate inhibitory effects that occur early in development.

Animals↗

Patterns of GFAP-immunoreactivity parallel the tonotopic axis in the developing dorsal cochlear nucleus.

The role of glia in the development of tonotopic and laminar organization in the auditory central nervous system has not been well characterized. In other systems, glia immunoreactive for glial fibrillary acidic protein (GFAP) appear to function in development of radial, laminar and topographic organization. Using a polyclonal antibody to GFAP, we have characterized the development of GFAP-immunoreactivity in the dorsal cochlear nucleus (DCN), a laminated and tonotopically organized central auditory system structure. Results suggest that in this nucleus, the GFAP-immunoreactive processes are not found within or between developing laminae, rather glial processes are observed parallel to presumptive isofrequency sheets before primary afferents have invaded the nucleus. Thus, GFAP-immunoreactive processes are positioned to play an early role in establishing the tonotopic axis of the DCN.

Animals↗

Structure and function of gustatory neurons in the nucleus of the solitary tract. I. A classification of neurons based on morphological features.

Prior investigations in other laboratories have provided convincing evidence that the neurons of the rostral nucleus of the solitary tract (rNST) can be grouped according to their physiological response properties or morphologic features. The present study is based on the premise that the response properties of gustatory neurons are related to, and perhaps governed by, their morphology and connectivity. In this first phase of our ongoing investigation of structure-function relationships in the rNST of the rat, we have used intracellular injection of neurobiotin to label individual physiologically characterized gustatory neurons. A total of 63 taste-sensitive neurons were successfully labeled and subjected to three-dimensional quantitative and qualitative analysis. A cluster analysis using six morphologic features (total cell volume, soma area, mean segment length, swelling density, spine density, and number of primary dendrites) was used to identify six cell groups. Subsequent analyses of variance and posthoc comparisons verified that each of these six groups differed from all others with respect to at least one variable, so each group was "typified" by at least one of the six morphologic features. Neurons in group A were found to be the smallest neurons in the sample. The cells in group B had small somata and exhibited the highest swelling density of any group. Group C neurons were distinguished by dendrites with long, spine-free branches. These dendrites were significantly longer than those of any other group except Group F. The neurons in group D had more primary dendrites than any other group. Group E neurons possessed dendrities with the lowest swelling density but the most spines of any group. The cells in group F were the largest neurons in our sample and possessed the largest somata of any group. Thus overall cell size and density of dendritic spines and swellings were found to be particularly important variables in this classification scheme. Our preliminary results suggest that the number and density of dendritic spines (as well as other morphologic features) may be related to a given neuron's most effective stimulus, indicating that it will indeed be possible to use the criteria established in the present investigation to derive structure-function relationships for gustatory neurons in the rNST.

Animals↗

A radial gradient of fibril density in the gerbil tectorial membrane.

The tectorial membrane plays a key role in the transduction of mechanical to neural energy in the inner ear. To better understand the transduction process the composition of the tectorial membrane needs to be elucidated. This study was done to determine if Type A collagen fibrils are distributed homogeneously in the tectorial membrane or if there are longitudinal or radial gradients of fibril concentrations. Our results suggest that while there is no longitudinal gradient, there is a radial gradient of fibril concentration. The concentration of fibrils in the limbal (inner) zone of the tectorial membrane exceeds that in the marginal (outer) zone in all cochlear locations examined. This gradient is most marked in the basal, high frequency coding region of the cochlea. While fibril gradients in the tectorial membrane have not been the focus of previous investigations, several findings by other authors support the proposition that the marginal zone of the tectorial membrane is more compliant than the limbal zone. This radial gradient of tectorial membrane stiffness is likely to contribute to the characteristics of movement of the cochlear partition.

Analysis of Variance↗

Development of gerbil outer hair cells after the onset of cochlear function: an ultrastructural study.

It has recently been proposed that elements which contribute to active cochlear processes develop at the same time (between postnatal day (PND) 12 and 21) as the shift of the place code in the developing gerbil cochlea. Since outer hair cells (OHCs) have been implicated in these processes, we have hypothesized that developing OHCs will exhibit changes in anatomical features that contribute to cochlear maturation. Our results demonstrate that the ultrastructural characteristics of OHCs change after the onset of hearing (PND 12), during the time that cochlear nonlinearities are being established (PND 12-21). Differences are primarily associated with the distribution of cytoplasmic organelles. The subsurface cisternae (SSC), which are thought to be related to the mechanical support of the outer hair cell, to cell motility, and therefore to cochlear mechanics, are present at PND 10 but remain immature, with cisternal layers added during the preweanling period. In immature OHCs, more mitochondria are centrally-located than in mature OHCs. During development mitochondria come to form a continuous row near the innermost leaflet of the SSC. These ultrastructural features undergo rapid change during the maturation of peripheral auditory function.

Animals↗

Distribution of actin in developing outer hair cells in the gerbil.

During the two weeks following the onset of cochlear function in the gerbil, active cochlear processes appear to mature. The active cochlear processes likely involve outer hair cells with their specialized lateral wall structures, including the subsurface cisternae and associated cytoskeletal elements. We have previously demonstrated that the subsurface cisternae mature gradually during the time that active cochlear processes mature in the gerbil. In the study reported here, we used postembedding immunocytochemical electron microscopy to investigate whether actin labelling associated with the cortical cytoskeleton of the gerbil outer hair cell increased concomitantly. In contrast to the gradual development of the subsurface cisternae, actin labelling in the region of the cortical cytoskeleton significantly increased during the onset of cochlear function and maintained this level during the time that active cochlear processes mature. Thus, it appears that increased actin adjacent to the lateral plasma membrane of the outer hair cell is related to the onset of cochlear function rather than to the maturation of active cochlear processes.

Actins↗

Changing patterns of peanut agglutinin labelling in the dorsal cochlear nucleus correspond to axonal ingrowth.

Various studies have suggested that glycoconjugates may influence connectivity and lamination in the developing central nervous system and may function as barriers to neuritic extension. It has been proposed that the peanut agglutinin lectin labels a glycoconjugate subserving a barrier function. We chose to investigate the distribution of this peanut-agglutinin-labelled glycoconjugate in the dorsal cochlear nucleus of the developing hamster since the development of the dorsal cochlear nucleus is well characterised and its axons obey laminar boundaries. The distribution of peanut agglutinin label throughout the cochlear nucleus delineated zones that cochlear axons fail to invade. In the dorsal cochlear nucleus, laminar differences were reduced on postnatal d 13 and virtually disappearing by postnatal d 23. Label in the molecular layer dissipated as axons and dendrites grew into this layer. These patterns of peanut agglutinin binding correspond to axonal ingrowth and are consistent with a barrier function for glycoconjugates in the molecular layer.

Animals↗

Actin distribution along the lateral wall of gerbil outer hair cells.

Outer hair cells can contract parallel to their long axis, and it has been hypothesized that actin may play a role in this contraction. In this study, actin distribution was examined in the gerbil organ of Corti using postembedment immunoelectron microscopy. In addition to regions typically labelled by actin antibodies and observed by epifluorescence--the cuticular plate, stereocilia, and supporting cell processes--these procedures preserved the ultrastructure of the cell and allowed us to demonstrate actin reactivity along the lateral wall of the outer hair cells between the subsurface cisterns and the plasma membrane. This region is the location of structures (pillars and cortical cytoskeleton) though to be associated with contraction of the outer hair cells.

Actins↗

Development of GAD-immunoreactivity in the dorsal cochlear nucleus of the hamster and cat: light and electron microscopic observations.

Physiologic and pharmacologic evidence suggests that inhibitory influences are active in the mammalian dorsal cochlear nucleus (DCN) by the onset of hearing, while anatomical evidence suggests that inhibitory synapses are not present until days or weeks later. One inhibitory neurotransmitter in the DCN is gamma aminobutyric acid (GABA) and its presence can be indexed by immunohistochemical localization of its synthetic enzyme glutamic acid decarboxylase (GAD). The present study investigated the ingrowth and synapse formation of GAD-immunoreactive inputs in the DCN of cat and hamster. GAD-immunoreactive puncta are present in the DCN of the cat at birth and of the hamster on postnatal day (PND) 3. Thus, the present data correlate well with the physiologic and pharmacologic evidence. In both species the first labelled puncta are near the dorsal acoustic stria and may originate from efferent axons in the stria. Several days later a band of labelled puncta is found in the fusiform cell layer. This location is equivalent to the termination zone of cartwheel cells, GAD-immunoreactive interneurons in the DCN. Based on this spatiotemporal sequence in the appearance of GAD-immunoreactive puncta, we suggest that sources of GABA extrinsic to the DCN mature first, followed by intrinsic sources.

Animals↗

Morphology of HRP-labelled cochlear nerve axons in the dorsal cochlear nucleus of the developing hamster.

To study the development of the central terminal arbors of the cochlear nerve fibers in the dorsal cochlear nucleus, horseradish peroxidase-labelled axons in young and adult hamsters were analyzed morphometrically. Brainstem slices with whole cochlear nuclei were maintained in a slice chamber and the cochlear nerve root was injected with a mixture of wheat germ agglutinin-horseradish peroxidase, horseradish peroxidase and poly-L-ornithine. The poly-L-ornithine was added to keep the injection site small; small injections resulted in only a few axons being labelled and permitted reconstruction of individual fibers. Axons underwent an initial period of ingrowth that was completed prior to the onset of hearing (postnatal day 16). After this time the morphology and area of influence of the axons remained unchanged but the nucleus continued to increase in size. Since no additional cochlear nerve axons grow into the nucleus during this period of nuclear growth, the existing axons necessarily become more widely spaced as development proceeds. These anatomical changes may contribute to the progressive narrowing of auditory cell tuning curves.

Acoustic Stimulation↗

Glutamate neurotoxicity in the developing rat cochlea: physiological and morphological approaches.

The neurotoxic effects of exogenous glutamate were studied in the rat cochlea. Glutamate-treated rats (4 g/kg/day i.p., postnatal days 2-9) exhibited electrophysiologically-measured elevations in high frequency thresholds usually associated with hair cell loss in the basal region of the cochlea. While surface preparations of the organ of Corti revealed no loss of hair cells, there was a dramatic and selective reduction of neurons in the basal, high frequency-related portion of the spiral ganglion. This sensitivity of developing spiral ganglion cells to the neurotoxicity of glutamate is consistent with the hypothesis that glutamate or a structurally related substance is a neurotransmitter at afferent synapses of cochlear hair cells.

Acoustic Stimulation↗