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I R Schwartz

Publications and source records attributed to I R Schwartz.

At least 19 recordsLinked to original sources
PubMed2000

Differential postsynaptic distribution of GluRs 1-4 on cartwheel and octopus cell somata in the gerbil cochlear nucleus.

Differences were demonstrated in the distribution of glutamate receptors (GluR) 1, 2, 2/3 and 4 postsynaptic immunoreactivity (PSIR) on the somata of cartwheel and octopus cells in the adult gerbil cochlear nucleus (CN). Montages of electron micrographs of cartwheel and octopus cells immunoreacted with antibodies to GluR 1, 2, 2/3 and 4 were prepared. The number of synaptic terminals with PSIR were counted on all cells for each antibody, normalized to the total length of somatic surface analyzed. The density of terminals apposed to PSIR on octopus cells was similar for the antibodies GluR1, 2/3 and 4, but significantly less for GluR2. On cartwheel somata the numbers of terminals apposed to immunoreactive postsynaptic specializations with GluR1, 2, 2/3 or 4 were not significantly different from each other. The density of terminals apposed to GluR2/3 and 4 positive postsynaptic specializations was significantly less on cartwheel cells than on octopus somata. The data suggest that the decreased presence of the GluR2 subunit, which confers calcium impermeability to the assembled receptor and slower gating kinetics to receptors with a high GluR4 content, is the major difference in the AMPA receptors on the somata of these cell types. The presence on cartwheel cells of a majority of AMPA receptors which contain GluR2 may account for the fact that cartwheel cells respond to shocks to the auditory nerve with 100 ms excitatory postsynaptic potentials (EPSPs), while octopus cells, most of whose AMPA receptors lack GluR2, respond with 1 ms EPSPs.

Animals↗
PubMed2000

Calcium binding proteins and the AMPA glutamate receptor subunits in gerbil cochlear nucleus.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. The GluR2 subunit confers calcium impermeability to AMPA receptors. Various calcium binding proteins play a role in calcium regulation within the neurons. This study sought to identify possible relationships between calcium binding proteins and glutamate receptor subunits, especially GluR2, in gerbil cochlear nucleus neurons. Our immunohistochemical observations reveal no particular correlation between GluR2 and calbindin; all the cell types show labeling for all the antibodies studied except calretinin. There was coincidence of strong GluR4 and strong parvalbumin staining in octopus cells, although calbindin was also present in these cells. This study suggests a possible relationship between parvalbumin and predominantly GluR4 containing receptors, even when calbindin is present. The absence of a strong inverse correlation between the presence of ionotropic AMPA receptor subunit GluR2 and calbindin suggests a more significant role of non-AMPA ionotropic glutamate receptors or other voltage-gated channels in the regulation of calcium in the neurons of cochlear nucleus. Alternatively, more detailed analysis of receptor composition at particular synapses and the subcellular localization of specific calcium binding proteins may be required.

Animals↗
PubMed1999

Development of GABA, glycine, and their receptors in the auditory brainstem of gerbil: a light and electron microscopic study.

Inhibitory synaptic transmission is known to play an important role during the maturation of central auditory pathways. While there is a lot of information on the modulatory role of glycine (Gly) on the postsynaptic target nuclei in the developing auditory brain stem, such a role for gamma-aminobutyric acid (GABA) in the lateral superior olive (LSO) of neonatal gerbil has been only recently reported (Kotak and Sanes [1997] Soc Neurosci Abst 23:1549; Kotak et al. [1998] J Neurosci 18:4646-4655). Here we present further immunohistochemical findings and the first ultrastructural evidence documenting a significant decrease in the postsynaptic localization of the beta2,3 subunit of the GABA(A) receptor from postnatal day (P)4 to P14 in the LSO of gerbil and the shift in the location of most of the staining from dendritic to astroglial over the same time course. There was a concomitant increase in staining for the Gly receptor (GlyR) anchoring protein, gephyrin. At the same time, GABA and Gly did not show a significant change in their staining pattern, suggesting that the transmitter levels are not particularly indicative of the inhibitory function in the neonatal gerbil LSO, but their receptors on the postsynaptic cells are. The observations of the present study suggest that the early GABAergic inhibition may be important in establishing appropriate synaptic contacts in the LSO of gerbil.

Animals↗
PubMed1999

Glutamate receptor subunits in neuronal populations of the gerbil lateral superior olive.

The distribution of AMPA-preferring ionotropic glutamate receptors (GluR) within the gerbil lateral superior olive (LSO) was investigated immunocytochemically using antibodies to GluR1, 2, 2/3 and 4. Light microscopy showed GluR1 antibody preferentially labeling a population of small neurons located in the dorsal hilus and a population mainly at or near the margins of the LSO. GluR4 antibody strongly stained most large LSO neuronal somata and proximal dendrites including all principal cells. GluR2/3 antibody showed very modest staining and appeared in most cell types. GluR2 showed less intense neuronal staining than GluR2/3 and was observed as a punctate accumulation at the surface of some neuronal profiles. GluR1, 2, 2/3 and 4 immunoreactivity was found along dendrites of most large LSO neurons and in their somata. Postsynaptic specializations positive for GluR2 were rare on LSO somata compared to the high frequency of GluR4 and 1 specializations. Double labeling studies showed that different portions of the distal dendrites showed a preponderance of GluR1 or GluR4 subunits. Electron microscopic observations confirm similarities in the localization of immunoreactivity for the antibodies tested in the cytoplasm of somata and dendrites, but reveal differences at the plasmalemma, at synaptic appositions and appositions with glial processes. Receptor composition varied with cell type and location on cells.

Animals↗
PubMed1998

A developmental shift from GABAergic to glycinergic transmission in the central auditory system.

GABAergic and glycinergic circuits are found throughout the auditory brainstem, and it is generally assumed that transmitter phenotype is established early in development. The present study documents a profound transition from GABAergic to glycinergic transmission in the gerbil lateral superior olive (LSO) during the first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical stimulation of the medial nucleus of the trapezoid body (MNTB), a known glycinergic projection in adult animals. GABAergic and glycinergic components were identified by blocking transmission with bicuculline and strychnine (SN), respectively. In the medial limb of LSO, there was a dramatic change in the GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12% at P12-P16. There was an equal and opposite increase in the glycinergic component during this same period. Direct application of GABA also elicited significantly larger amplitude and longer duration responses in P3-P5 neurons compared with glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons were more sensitive to SN throughout development. Consistent with the electrophysiological observations, there was a reduction in staining for the beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine receptor-associated protein gephyrin increased. Brief exposure to baclofen depressed transmission at excitatory and inhibitory synapses for approximately 15 min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data demonstrate a striking switch from GABAergic to glycinergic transmission during postnatal development. Although GABA and glycine elicit similar postsynaptic ionotropic responses, our results raise the possibility that GABAergic transmission in neonates may play a developmental role distinct from that of glycine.

Aging↗
PubMed1998

Development of N-methyl-D-aspartate receptor subunit immunoreactivity in the neonatal gerbil cochlear nucleus.

The distribution of immunoreactivity for the ionotropic N-methyl-D-aspartate (NMDA) receptor subunits was mapped in the cochlear nucleus of postnatal day (P) 7, P14, P21, and P28 gerbils. Frozen sections and serial plastic sections of tissue were incubated with antibodies to NMDAR1 (NR1), NMDAR2A (NR2A), NMDAR2A/B (NR2A/B), and NMDAR2B (NR2B). An overall diffuse stain was noted at P7 for NR1 and NR2A/B. Staining of neuronal somata in the dorsal cochlear nucleus molecular layer and fusiform cell layer, the posteroventral cochlear nucleus octopus cell area, and the anteroventral cochlear nucleus increased from P7 to P28. Staining of the neuropil (the unresolved mass of processes and axons, excluding only neuronal somata and distinctly stained proximal dendrites) of the deep dorsal cochlear nucleus and posteroventral cochlear nucleus showed a steady decrease, while molecular layer neuropil remained moderately stained. The NR2A antibody produced a distinctive staining of dendrites in the dorsal cochlear nucleus deep and fusiform cell layers seen first at P14 with increasing dendritic lengths stained at P21 and P28. Giant neurons of the deep dorsal cochlear nucleus were the most conspicuous somata stained by the NR2A. Their stained dendrites spanned much of the dorsal cochlear nucleus deep and fusiform cell layers and even extended into the octopus cell area of the posteroventral cochlear nucleus. Dendritic staining was also present in caudal and rostral posteroventral cochlear nucleus, first distinguishable at P14 and becoming increasingly strong. The Chemicon polyclonal NR2B antibody produced glial staining especially prominent in the caudal posteroventral cochlear nucleus and the dorsal cochlear nucleus fusiform cell layer, most intense at P7 and subsequently decreasing, although not disappearing, in all areas through P28. The Molecular Probes (Eugene, OR) polyclonal NR2B produced a light granular staining pattern over a number of somata but no glial staining. Neuropil staining was not prominent with either NR2B antibody. Differences in changes of neonatal immunoreactivity patterns in different populations of cochlear nucleus neuronal somata and dendrites for NR1, NR2A, NR2A/B, and NR2B suggest that alterations in some receptor composition is occurring over the period spanning the onset of hearing.

Animals↗
PubMed1997

In vitro induction of microcyst-like structures in the superior olivary complex.

To investigate the etiology of hole formation in the gerbil and rat central auditory system, organotypic cultures were grown in control and veratridine-containing media. The latter condition is known to increase neuronal activity. Tissue was obtained at postnatal day 6 and grown for 6-9 days in vitro, a period prior to the formation of holes in vivo. In both rats and gerbils, veratridine led to the appearance of large numbers of holes, and these were phenotypically similar to those found in vivo. These results support the idea that hole formation is an activity-dependent phenomenon, and suggest that it is not restricted to the mature gerbil auditory system.

Animals↗
PubMed1993

Glial or neuronal origin of microcysts in the gerbil PVCN?

This study used immunocytochemical markers for various classes of glial cells to investigate the relationship between glial elements and microcysts in the gerbil auditory system at the light and electron microscopic level. Monoclonal antibodies S-100, GFAP and Rip were used on tissue from 3- and 12-month old animals and acutely deafened 12 month old animals to localize astrocytes and oligodendrocytes and their processes around microcysts. No differences in the number and distribution of astrocytes were found in the PVCN as a result of aging or deafening. S-100 and GFAP labeling showed a high correlation between astrocytic processes and microcysts. The results indicate that up to 80% of microcysts are either contacted by astrocytic profiles over much of their perimeter or are labeled internally by the astrocytic markers S-100 or GFAP. Some microcysts appear to originate in neuronal dendrites or in axons.

Animals↗
PubMed1992

Selective retrograde transport of nipecotic acid, a GABA analog, labels a subpopulation of gerbil olivocochlear neurons.

Perfusion of the gerbil cochlea with micromolar quantities of 3H-gamma-aminobutyric acid (GABA) results in rapid, selective labeling of 50-60% of the olivocochlear (OC) efferent terminals on afferent dendrites beneath the inner hair cells, and all of the efferent terminals beneath the outer hair cells. In order to identify the neurons from which these GABA-accumulating terminals originate, the cell bodies were localized by using retrograde transport of 3H-nipecotic acid, a metabolically inert GABA analog. With survival times of 6-30 hours after cochlear injection, myelinated OC efferent fibers and cell bodies were well labeled, with the greatest number being labeled at 12-18 hours. All of the labeled neurons belonged to the medial OC system, and no lateral OC neurons were labeled. It is concluded that the GABA-accumulating endings in the gerbil cochlea arise from medial OC neurons, and therefore that medial OC efferent neurons in this species project to both inner and outer hair cell regions.

Animals↗
PubMed1991

Neuronal populations in the gerbil PVCN: effects of age, hearing status and microcysts.

This study was designed to test the hypothesis that microcysts in the gerbil auditory system are formed from neuronal somata. Six neuronal types (octopus, multipolar, bushy, elongate, miscellaneous and small) were distinguished, counted and measured along with the microcysts in the posteroventral cochlear nuclei (PVCNs) of 3, 12 and 36 month old gerbils. No decrease was observed in the numbers of neurons in any neuronal class, or in the neuronal population as a whole, in the PVCN of the gerbil as a function of age. Neither was any change observed in the PVCN area occupied by non-neuronal, non-microcyst elements. Neuronal sizes were unchanged between 3 and 12 months, but multipolar and bushy cells, as well as the total neuronal population decreased significantly in size between 12 and 36 months. The number and size of microcysts increased significantly between 3 and 12 months of age and accounts for increases in PVCN volume. The number and size of microcysts decreased significantly between 12 and 36 months. Thus, the appearance of microcysts can not result from the selective loss of any single class of neurons. Hearing was assessed in five 36 month old animals with auditory brainstem responses (ABR) and number and size of microcysts were found to correlate with hearing status, being largest and most numerous in animals with the best hearing, and smallest and fewest in the deaf animal. It is concluded that microcysts cannot represent a neurodegenerative disease of neuronal somata. Microcyst formation appears to be a dynamic process related to the degree of auditory stimulation.

Aging↗
PubMed1990

Collaterals from lateral and medial olivocochlear efferent neurons innervate different regions of the cochlear nucleus and adjacent brainstem.

Two populations of superior olivary neurons which project to different sensory cell regions in the cochlea also give off collateral projections to the ventral cochlear nucleus (VCN) and adjacent brainstem. To determine whether these VCN projections also have different targets they were characterized by selective retrograde amino acid transport. Retrograde transport of 3H-d-aspartate (D-ASP) selectively labeled the unmyelinated fibers and neurons of the lateral olivocochlear (OC) system including a dense collateral projection to the central VCN. Retrograde transport of 3H-nipecotic acid (NIP) labeled the myelinated fibers and neurons of the medial OC system, including collateral projections to the peripheral VCN, subpeduncular granule cells, and nucleus Y. Medial and lateral OC efferent collaterals thus innervate different regions of the CN. Lateral system collaterals overlap extensively with Type I spiral ganglion cell afferent input. They are well positioned to play a role in modulating afferent input to the central auditory system, as is the primary projection of these efferents to the cochlea. The medial system collaterals project near the recently described afferent projections of Type II spiral ganglion cells. The medial system collaterals may therefore be related to the function of outer hair cells, as the medial system primary axons appear to be in the cochlea.

Animals↗
PubMed1990

Autoradiographic studies of selective amino acid uptake by neural and nonneural elements in the gerbil cochlea.

The cochlea is well suited for studies of the uptake properties of auditory neurons and nonneuronal supporting cells. Probe concentrations of radioisotopically labeled amino acids, including putative neurotransmitters and their precursors, breakdown products, and blockers, can be introduced via the natural, fluid-filled channels of the inner ear. Uptake patterns can be mapped at cellular and intracellular levels using light and electron microscopic autoradiographic methods. The procedures for introduction of label, fixation, plastic embedment, and light and electron microscopic autoradiography are described with special reference to the cochlea. Labeling patterns observed with over 20 amino acids are summarized for hair cells, spiral ganglion neurons, efferents, and nonneural elements of the stria vascularis, limbus, and modiolus. Limitations on the interpretation of results and their implications for the general usefulness of the methods are discussed.

Amino Acids↗
PubMed1990

Safety of predeposit autologous blood donation in the third trimester of pregnancy.

The option of predeposit autologous blood donation (PABD) before elective surgery has been gaining popularity as a means of eliminating the transmission of the acquired immune deficiency syndrome and hepatitis. It also prevents potential antigen sensitization and transfusion reactions. The use of PABD in pregnant women has been described, but its safety for both mother and fetus, especially in the first and third trimester, has not been established. After studying 16 third-trimester pregnant women with antenatal surveillance techniques and continuous fetal monitoring, we concluded that PABD is a safe procedure for both mother and fetus.

Adult↗
PubMed1989

Anatomic and physiological correlates in bullfrog vestibular nerve.

1. The correlations between anatomic and physiological characteristics of primary afferent neurons innervating the anterior semicircular canal in the bullfrog were investigated. These characteristics were examined separately in large groups of neurons, and the direct correlations between them were established in a subset of neurons by means of intraaxonal recording and labeling. 2. Anatomic features of the anterior canalicular nerve that were related with fiber diameter were studied. This nerve was composed of an average of 1,142 fibers (standard deviation of 171 in 5 samples), of which 42% were less than 2 microns in diameter and 8% were greater than 7 microns. The nerve branched into 6 clearly defined bundles, whose fiber diameter-dependent composition could be determined in 5 samples. In the 2 center bundles, 32% of the fibers had diameters greater than 7 microns. In contrast, these thick fibers comprised only 4% of the fiber population in the 2 lateralmost bundles, in which 44% of the fibers had diameters less than 2 microns. The projections of labeled afferent fibers were traced into the neuroepithelium, and it was demonstrated that all thick fibers, even those of the lateral bundles, turned toward more central regions of the crista. Consequently, in the bullfrog, there is a clear predominance of thick afferent fibers innervating the anterior crista's central region and thin fibers in the peripheral region. 3. The dendritic morphology of the broad classes of afferent fibers (i.e., thick and thin) was elucidated. Individually labeled thick afferents possessed dendrites forming short, thick, clawlike extensions to contact a few hair cells. The thinnest afferents were labeled through extracellular horseradish peroxidase (HRP) injections. In contrast to the thick fibers, thin afferents were characterized by an unbranched trajectory with serially located bouton-like structures that were apposed to successive hair cells. 4. The characteristics of spontaneous firing and the responses to rotational stimuli were determined for 138 anterior canalicular neurons. Spontaneous firing rates ranged from 0 to 95 spikes.s-1. The coefficient of variation (CV) of spontaneous firing ranged from 0.12 to 2.5. Response gains to high- (0.5 and 0.4 Hz) and medium- (0.05 Hz) frequency sinusoidal acceleration stimuli were positively correlated with CV (P less than 0.001) for neurons with a CV value less than or equal to 0.5. The gain of neurons characterized by more irregular spontaneous firing (CV values greater than 0.5) was uncorrelated with CV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

An improved flat embedding technique for immunoelectron microscopy.

Immunocytochemical staining has been widely used for localizing various hormonal antigens, protein markers and putative neurotransmitters in tissues. Immunostained sections can be examined light microscopically and specific areas selected for electron microscopic study.

Histological Techniques↗
PubMed1988

Alteration in osteoblast activity and nutritional vitamin-D deficiency in non-hypercalcemic malignancy.

The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca2+), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24 +/- 0.70 SE vs. 11.50 +/- 2.20 ng/ml; P less than 0.005). Patients on corticosteroids had lower 1,25(OH)2D values than controls (18.81 +/- 2.71 vs. 27.83 +/- 1.17 pg/ml; P less than 0.01), whereas those not on corticosteroids had normal 1,25(OH)2D values. These results suggest that patients with nonhypercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)2D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function.

Aged↗
PubMed1988

Ultrastructural characterization of gerbil olivocochlear neurons based on differential uptake of 3H-D-aspartic acid and a wheatgerm agglutinin-horseradish peroxidase conjugate from the cochlea.

Two populations of olivocochlear (OC) neurons have been identified in the gerbil brain stem on the basis of differential labeling patterns of 3H-D-aspartic acid (D-ASP) and wheatgerm agglutinin-horseradish peroxidase conjugate (WGA/HRP) from the cochlear perilymph. While both populations are capable of uptake and retrograde uptake of WGA/HRP, one population accumulates and retrogradely transports D-ASP (D-ASP OC neurons) and the other does not (non-D-ASP OC neurons). D-ASP OC neurons are found in or near the lateral superior olive, are small in size, and receive very few synaptic contacts. The vast majority of these synapses contain small, mildly pleomorphic vesicles with scattered dense core vesicles. Synapses with distinctly larger pleomorphic vesicles have also been observed. These neurons possess all of the features common to neurons of the lateral olivocochlear system. Non-D-ASP OC neurons are found primarily in the ventral nucleus of the trapezoid body, as well as in the area between the medial superior olive and the medial nucleus of the trapezoid body. These neurons are larger and receive greater numbers and types of synaptic contacts than those found on D-ASP OC neurons. The 2 most common synapses found on non-D-ASP OC neurons are axosomatic ones containing small, mildly pleomorphic vesicles and scattered dense core vesicles similar to those seen on the D-ASP OC neurons, and axodendritic synapses containing large, round vesicles. Much less frequently observed are synapses containing small, round vesicles or ones containing predominantly flat vesicles. The ultrastructural features of the non-D-ASP OC neurons correspond to those described for neurons of the medial olivocochlear system.

Animals↗