Biomedical subjects

S Jhaveri

Publications and source records attributed to S Jhaveri.

At least 55 records · Page 3Linked to original sources

PubMed1990

Transient patterns of GAP-43 expression during the formation of barrels in the rat somatosensory cortex.

The development of the rat barrel field cortex was investigated with an antibody to the axonal membrane-specific phosphoprotein GAP-43 in order to examine the developmental pattern of afferent projections, and with cytochrome oxidase histochemistry and Nissl stains to reveal the morphogenesis of cortical barrels. On the first two days after birth, GAP-43 immunostaining in the cortical plate was light and diffuse, then became intense in the presumptive layer IV of the parietal cortex on PND3 (day of birth = PND0). Immunoreactive densities were visible as small, focal patches within the centers of prospective barrels. These densities increased in size and intensity over the next few days and then diminished abruptly. On PND7, the distribution of GAP-43 was coextensive with barrels, as defined by cytochrome oxidase histochemistry and Nissl staining. GAP-43 virtually disappeared from the barrels after PND7. From the second postnatal week, GAP-43 immunostaining was evident in the septa between barrels and in the dysgranular regions of SI cortex. This pattern of GAP-43 distribution was complementary to the pattern of cytochrome oxidase activity, and persisted into maturity. In an attempt to identify possible source(s) of GAP-43 positive afferents in the developing barrels, we examined the effects of altering the sensory periphery on the distribution of GAP-43 immunostaining in the cortex. Rat pups had row C whiskers cauterized on PND0 and were sacrificed on PND3 or PND5. Whereas immunopositive densities corresponding to intact whiskers developed in a normal, punctate pattern, cortical representation of the lesioned whiskers formed a continuous band of labeling that was evident as early as PND3. We argue that the disjunctive expression of GAP-43 in the barrel field reflects the pattern of distribution of afferents (most likely from the ventro-basal thalamic nucleus) to the barrel field cortex, and that this pattern may be instructive in the formation of barrels as cytoarchitectonic units. The rapid alteration in patterns of immunostaining following whisker lesions lends further support to the conclusion that the "barrel template" is conveyed to the neocortex by incoming afferents. The possible significance of the transient expression of GAP-43 in the maturing barrel field is discussed.

Aging↗

PubMed1990

Phorbol ester-mediated induction of HIV-1 from a chronically infected promonocyte clone: blockade by protein kinase inhibitors and relationship to tat-directed trans-activation.

Potent inhibitors of protein kinases C and A, including 1-(5 isoquinolinyl sulfonyl) 2-methyl piperazine (H7), staurosporine, and 2-aminopurine, depressed phorbol ester-induced HIV-1 virion production and HIV-specific transcripts by greater than 90% in chronically infected promonocytic cells. Suppression was dose-dependent and occurred at concentration that had little effect on cell growth. These effects appeared to be specific to activation of the PKC-diacylglycerol system. They did not alter IUdr-mediated induction of HIV. In addition, PMA enhancement of an HIV-LTR driven reporter gene was not blocked by H7 in the presence or absence of exogenous tat, at concentrations capable of inhibiting upregulation of virus at the cellular level. Insight into the biochemical mechanisms of these processes is critical to understanding interactions of HIV with the immune system, and may eventually uncover new therapeutic strategies.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1990

Use of brainstem flat-mounts for visualizing DiI-filled axons in the developing rodent visual system.

The lipophilic carbocyanine fluorescent label DiI was injected in one eye of aldehyde-fixed embryonic or postnatal hamsters and the brains were examined using flat-mounts of the chiasm region, of the lateral surface of the brainstem, or of the midbrain tectum. Single axons could be discerned within the optic nerves and along the optic tract. Many fibers were tipped by growth cones, ending at various levels of the brainstem. Fine details of retinofugal axon morphology, including varicosities, branch-points and filopodial extensions on growth cones were visible in the flat-mounts. Such preparations allow a high-resolution view of labeled axons which course near the surface of the brain. It is possible, with this method, to simultaneously examine the morphogenesis of multiple collateral arbors on single fibers which project to more than one terminal zone.

Animals↗

PubMed1990

Neurogenesis and development of callosal and intracortical connections in the hamster.

The developmental time-course of callosal and ipsilateral corticocortical projections was studied in embryonic and postnatal hamsters, from the time of neurogenesis until the appearance of adult patterns. Callosal neurogenesis was determined by combining the incorporation of [3H]thymidine injected on specific embryonic days with retrograde labelling of callosal neurons in the adult animal. The development of both callosal and corticocortical projections was studied by the transport of wheat germ agglutinin conjugated to horseradish peroxidase. Despite a significant radial disperson of postmigratory neurons born on the same day, it was found that the birthdates of callosally-projecting neurons in the frontal cortex were not restricted to a short period of time, but extended between embryonic days 13 and 15. This period covers the neurogenesis of cells in cortical layers III-V. Elongation of callosal axons (and possibly also of corticocortical fibres) started a couple of days before birth in the frontal cortex, and continued through the first postnatal days. After a "waiting period" of a few days, axons from both sets of projections were seen innervating restricted target sectors of the cortex. The zones of origin of these projections were initially exuberant, but were subsequently trimmed to overlap completely with the corresponding terminal fields. It is concluded that callosal and ipsilateral corticocortical projections undergo similar sequences of ontogenetic stages, suggesting that the development of neocortical connectivity as a whole may be governed by one and the same set of rules.

Animals↗

PubMed1989

Immunohistochemical localization of GAP-43 in the developing hamster retinofugal pathway.

Metabolic labeling studies have shown that the developing hamster retinotectal pathway is marked by a high level of synthesis and axonal transport of the neuron-specific phosphoprotein GAP-43, which then decline sharply with synaptic maturation. To understand better the relationship of GAP-43 to specific developmental events, we used a monospecific antibody to examine the location of this protein in the optic tract and retinal target areas at various stages. In late embryonic and in neonatal hamsters, dense GAP-43 immunostaining was seen along the entire extent of the optic tract axons, including fascicles coursing over and through the lateral geniculate body (LGB) and within the upper layers of the superior colliculus (SC). The retinal origin of many of these fascicles was confirmed by their rapid disappearance after removal of the contralateral eye. During the first postnatal week, immunostaining in the fiber fascicles showed a marked decline, though the protein was still present throughout the neuropil of the LGB and SC. In the second postnatal week, the neuropil staining also diminished, and by 12 days after birth, both structures showed only light immunoreactivity. The high levels of GAP-43 in embryonic and neonatal optic tract axons coincide temporally with axon elongation, initial target contact, and collateral formation by the retinofugal fibers, whereas subsequent concentration of the protein in the neuropil suggests its involvement in the elaboration of terminal arbors and synaptogenesis.

Aging↗

PubMed1989

Peripheral nerve regeneration induces elevated expression of GAP-43 in the brainstem trigeminal complex of adult hamsters.

A polyclonal antibody was used to delineate the pattern of GAP-43 expression in central processes of trigeminal ganglion cells while their peripheral processes were undergoing regeneration. Two weeks after transection of the infraorbital nerve, levels of GAP-43 ipsilateral to the transection were greatly increased along the trajectory of infraorbital axons in the central trigeminal tract and also within the target neuropil. We conclude that elevated levels of GAP-43 in central processes of injured trigeminal ganglion cells occur in direct response to the regenerative response of the cell body and may have important implications for 'plasticity'-related changes seen in the adult trigeminal system.

Animals↗

PubMed1988

Sharpening of topographical projections and maturation of geniculocortical axon arbors in the hamster.

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.

Animals↗

PubMed1988

Distribution of morphologically different retinal axon terminals in the hamster dorsal lateral geniculate nucleus.

Afferent terminal arbors in the hamster LGBd were labelled with horseradish peroxidase (HRP) implanted into the optic tract. Three morphologically distinct terminal types, each with a different regional distribution, were observed. Type R1 terminals are large, ovoid swellings and are predominantly distributed medially within the nucleus. Type R2 terminals are very small, clustered varicosities and are distributed laterally and ventrally. Type R3 terminals are medium in size and their distribution overlaps with that of Type R1 and R2 terminals.

Afferent Pathways↗

PubMed1988

Visualizing anterogradely transported HRP by use of TMB histochemistry: comparison of the TMB-SNF and TMB-AHM methods.

Horseradish peroxidase (HRP), a commonly used enzymatic marker for tracing pathways in the central nervous system, can be visualized histochemically with the aid of the chromogen tetramethyl benzidine (TMB). In a recent report, Olucha and collaborators (J Neurosci Meth 13:131, 1985) introduced the use of ammonium heptamolybdate (AHM) as a substitute for sodium nitroferricyanide (SNF) which serves to stabilize the HRP reaction product. This TMB-AHM method of Olucha et al. proves superior to the TMB-SNF method of Mesulam (J Histochem Cytochem 26:106, 1978) in that the reaction does not produce crystalline artifact. For visualization of retrogradely transported HRP, the two methods are reportedly equivalent in sensitivity. In the work reported here, we have compared the sensitivity of the two methods in detecting HRP that was transported anterogradely after intraocular injections of the enzyme in normal adult and neonatal hamsters, as well as in animals with lesions of the superior colliculus or retina. We demonstrate that the TMB-SNF method is decidedly more sensitive than the TMB-AHM technique for visualization of anterogradely transported HRP. This difference in sensitivity is especially evident in regions of sparse projections.

Animals↗

PubMed1988

Changes in rapidly transported proteins in developing hamster retinofugal axons.

Proteins synthesized in retinal ganglion cells and conveyed to the terminals of optic tract axons in the rapid phase of axonal transport were analyzed at different developmental stages in the hamster. Animals between 2 d of age and adulthood were labeled intraocularly with 35S-methionine, and after a 4 hr survival time, the superior colliculus was dissected out, subjected to subcellular fractionation, and radiolabeled proteins in the particulate fraction analyzed by 2-dimensional gel electrophoresis and fluorography. The previously identified growth-associated phosphoprotein, GAP-43 (GAP-48, B-50, F1, pp46), was synthesized and transported at high levels in the neonate, but these levels declined precipitously after the second postnatal week. Immunohistochemical studies using a monospecific antibody showed that GAP-43 was localized along the entire length of retinal axons in the optic tract and target areas in P2 animals but was virtually absent in the adult visual pathway. By metabolic labeling, 2 proteins with molecular weights of about 230 kDa also showed a sharp decrease during development. In contrast, acidic proteins of 27 and 64 kDa, which were barely detectable in the neonate, increased steadily to become the most heavily labeled proteins of rapid axonal transport by the second postnatal week. Another group of proteins, of about 94-110 kDa, also rose to peak levels after birth but then declined. Temporal correlations between the molecular changes described here and the known anatomical events in optic tract development suggest that the synthesis and transport of particular membrane proteins may be directly related to the sequence of morphological changes.

Animals↗

PubMed1988

The development of callosal and corticocortical innervation in the neocortex of the hamster.

The development of cortical afferentation by callosal and ipsilateral corticocortical fibers was studied in hamsters by transport of wheat germ agglutinin conjugated to horseradish peroxidase. Elongation of callosal axons (and possibly also of corticocortical fibers) started a couple of days before birth and extended through the first postnatal days. After a "waiting" period of a few days, axons were seen innervating restricted target sectors of the cortex. The zones of origin of these projections were initially exuberant, but they were subsequently trimmed down to overlap with the corresponding terminal fields.

Afferent Pathways↗

PubMed1987

Enhanced visualization of axonally transported proteins in the immature CNS by suppression of systemic labeling.

In the neonate hamster, visualization of axonally transported proteins in the retinofugal pathway is obscured by high levels of systemic (background) labeling. Radiolabeled precursors injected into the eye diffuse rapidly into the general circulation and then across the immature blood-brain barrier to be incorporated into proteins that are synthesized throughout the brain. Systemic labeling can be suppressed, however, by i.p. injections of large amounts of either non-radioactive methionine 30 min after intraocular labeling with [35S]methionine, or non-radioactive leucine given at the time of intraocular labeling. Whereas the former competes with the radioactive precursor during incorporation into brain proteins (after most of the retinal labeling has already been achieved), the latter competes at the earlier stage of access to the brain. Both methods reduced background labeling by more than 60%, thereby allowing for unambiguous identification of axonally transported proteins. The pattern of rapidly transported proteins was found to be strikingly different between neonates and mature animals, including marked changes in an identified 'growth-associated protein' (50 kDa, pI 4.8).

Amino Acids↗

PubMed1984

Arthroscopy.

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Arthroscopy↗

PubMed1984

Anatomical basis of specific connections between sensory axons and motor neurons in the brachial spinal cord of the bullfrog.

The anatomical basis for the specificity of the monosynaptic stretch reflex has been studied in the brachial spinal cord of bullfrogs. Sensory axons from the triceps brachii muscle innervate the corresponding triceps motoneurons but do not innervate two types of unrelated motoneurons (subscapularis and pectoralis) (Lichtman, J.W., and E. Frank (1984) J. Neurosci. 4: 1745-1753). Retrograde labeling of these three types of motoneurons with horseradish peroxidase (HRP) demonstrated that their cell bodies had overlapping distributions in the lateral motor column, and their dendrites all occupied the same region of the dorsal horn. In addition, triceps sensory axons aborized extensively in the dorsal horn throughout the brachial spinal cord, with no obvious predilection for the region of the triceps motoneurons. Thus, the physiological specificity of these sensory-motor connections was not apparent from the anatomical location of the sensory or motor neurons. However, by injecting single pairs of related or unrelated sensory and motor cells with HRP, we found that related pairs formed anatomical contacts with each other more frequently than unrelated sensory-motor pairs did. These observations suggest that the specificity of these connections is most likely the result of local interactions between sensory and motor processes.

Animals↗

PubMed1983

Central projections of the brachial nerve in bullfrogs: muscle and cutaneous afferents project to different regions of the spinal cord.

The central projections of muscle and cutaneous sensory neurons in the bullfrog were labeled by filling their peripheral axons in the forelimb with horseradish peroxidase (HRP). Muscle afferent fibers were found to project exclusively to the ventral neuropil of the brachial spinal cord in the intermediate gray zone. Cutaneous afferent axons had their arbors limited to the dorsal neuropil. There is therefore a topography in the central representation of two classes of sensory modalities.

Animals↗

PubMed1982

Neuronal architecture in nucleus magnocellularis of the chicken auditory system with observations on nucleus laminaris: a light and electron microscope study.

This report presents the major structural features of neurons and their afferent input in nucleus magnocellularis, the avian homologue of the mammalian anteroventral cochlear nucleus. Results of light-microscope observations, as seen in Golgi, Nissl, and normal fiber preparations, as well as ultrastructural morphology are reported. In addition, cells and axons in nucleus laminaris, the presumed homologue of the mammalian medial superior olivary nucleus, are also described. In Golgi-impregnated material, the mature principal cell in nucleus magnocellularis has an ovoid soma encrusted with somatic spines. A dendrite, when present, emerges from the cell soma, travels for a short distance and breaks into a tuft of stubby terminal branches. Foremost among the afferents to nucleus magnocellularis are auditory nerve axons that terminate in large, axosomatic endings, or end-bulbs, covering a large portion of the somatic surface. Other afferents, which also end in relation to the perikaryon, are of undetermined and perhaps multiple origins. The neurons resemble the bushy cells of the mammalian anteroventral cochlear nucleus. Evidence is presented that individual axons from the nucleus magnocellularis bifurcate and send branches to the nucleus laminaris bilaterally, thus placing constraints on the binaural interactions possibly involved in lateralization functions. In electron micrographs, the end-bulbs appear as large, elongate structures which can cover a third of the cell soma. Multiple sites of synaptic specialization occur along these terminals. The synaptic membrane complexes may form directly on the cell body or on the sides or crests of somatic spines. These complexes are characterized by asymmetric membrane densities with a cluster of clear, spherical vesicles on the axonal side. Other small terminal profiles are also present on the somata receiving the end-bulbs. Dendritic profiles are scarce, in agreement with observations in Golgi impregnations. The structural findings indicate that the medial part of the nucleus magnocellularis is homologous to the anterior part of the mammalian anteroventral cochlear nucleus in that the neurons of nucleus magnocellularis are homologous to the bushy cells of the cat. On this basis, the cells in nucleus magnocellularis could faithfully preserve the acoustic response patterns generated in the auditory nerve. This should, in turn, allow a secure relay of bilateral latency differences essential for binaural interactions in the nucleus laminaris.

Animals↗

PubMed1982

Sequential alterations of neuronal architecture in nucleus magnocellularis of the developing chicken: a Golgi study.

Nucleus magnocellularis in the chicken consists predominantly of a population of medium-sized cells which receive large, axosomatic endings from the auditory nerve. The morphological development of these cells and their auditory input were studied with the Golgi methods. At 7 1/2-9 days of incubation (embryonic days 7 1/2-9, staged according to the Hamburger-Hamilton series), cells in nucleus magnocellularis have several long, branched dendrites, which often end in bulbous swellings. By embryonic day 10, efferent axons have already grown out from the cells and characteristic terminal plexuses of these axons are seen in nucleus laminaris bilaterally. The dendrites of cells in nucleus magnocellularis have been replaced by a multitude of long somatic processes, giving the cell body a shaggy appearance. This arrangement is maintained up to embryonic day 15, when a remarkable second transformation occurs. The cells lose their somatic processes and present bald, round profiles. Around embryonic days 17-18 a primitive-looking process with a tip like a growth cone emerges from the cell body and somatic spines are evident. By days 19-20, one or two thin, frail dendritic processes can be seen. Correlated with this dramatic series of changes in the cells is a fixed sequence of transformations of the incoming axons. Around embryonic day 10, primary sensory axons in nucleus magnocellularis end in swellings resembling growth cones. Between days 11 and 13, following the explosive growth of somatic processes there is a corresponding expansion and ramification of the auditory nerve endings. On embryonic day 14, there is a condensation of the terminal axon branches, which now form a compact, highly branched plexus. Between days 16 and 17, the plexus coalesces into a calycine structure, now approaching its final form, the end-bulb of Held, which is achieved by embryonic days 19-20. The transformation of the plexus to the calycine form occurs around the same that the cell loses its somatic processes. The parallel sequence in the morphogenetic stages of the assembly of the end-bulbs and their target cells evinces a correlation, if not a causal relationship between the sensory axons and the developing neurons. The arrangement of the somatic processes and axonal branches during the early, multipolar stage would provide an opportunity for optimum interactions between the synaptogenetic processes of the afferent axons and the target cells. The later morphological transformations could orchestrate the specific, cell-to-cell interactions which accompany, or even depend on the activity of the definitive end-bulb synapse.

Animals↗

PubMed1982

Sequential alterations of neuronal architecture in nucleus magnocellularis of the developing chicken: an electron microscope study.

The development of the auditory nerve endings and their target cells in nucleus magnocellularis was studied by electron microscopy of perfusion-fixed brains from embryonic day 12 to hatching. Embryonic days 12-13: somatic processes extend from the perikaryon. The cytoplasm of the soma and processes contains free ribosomes, mitochondria, lysosomes, rough endoplasmic reticulum, Golgi apparatus and an eccentric, heterochromatic nucleus. Small profiles of auditory nerve fibers containing round, clear vesicles make specialized contacts, including some synapses, on distal somatic processes but rarely on proximal somatic processes or on the soma. The postsynaptic zones contain a flocculent matrix. Days 15-17: somatic processes disappear and occasional attachment plaques are seen between cell bodies. The nucleus appears euchromatic. Cytoplasmic organelles form a dense matrix indicative of intense metabolic activity. Somatic spines are evident. The afferent axons form large, vesiculated profiles located, increasingly, on the cell body and somatic spines, with many points of synaptic contact. Opposite each ending a band of amorphous, flocculent material fills the postsynaptic cytoplasm. Embryonic day 18-hatching: the somatic cytoplasm becomes less dense; stacks of rough endoplasmic reticulum start to condense. Afferent axon terminals mature, especially the synaptic membrane complex and associated densities. The postsynaptic flocculent material diminishes in extent until it is found associated only with somatic spines. The ultrastructural observations on the maturation of nucleus magnocellularis closely corroborate and extend previous results with the Golgi methods. Developing auditory nerve fibers initially synapse on the distal parts of the somatic processes of the immature cells. As the somatic processes disappear or retract, axonal endings move to the soma and develop into large axosomatic end-bulbs. Possibly, the somatic processes as they retract drag the auditory nerve endings to the cell body. The findings also suggest a role of the transiently appearing, flocculent material of the postsynaptic regions in the formation of synapses.

Animals↗