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J S Kauer

Publications and source records attributed to J S Kauer.

At least 37 records · Page 2Linked to original sources

Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus.

We have used a replication-incompetent retrovirus to analyze the lineage of olfactory receptor neurons in young rats. At 5-40 days after infection, clusters of infected cells comprised two major types: one consisted of 1-2 horizontal basal cells, and a second consisted of variable numbers of globose basal cells and immature and mature sensory neurons. Olfactory nerve lesion (which enhances neuronal turnover) increased the frequency of the globose-sensory neuron clusters as well as the number of cells in such clusters. No clusters contained both horizontal and globose basal cells, and none contained sustentacular cells. These data suggest, at least in young rats, that horizontal basal cells are not precursors of olfactory neurons, that there is a lineage path from globose cells to mature neurons, and that sustentacular cells may arise from a separate lineage.

Animals↗

Lineage analysis of the olfactory epithelium using a replication-incompetent retrovirus.

We have analysed the lineage of olfactory receptor neurons using a replication-incompetent retrovirus injected beneath the olfactory epithelium of young rats. There are two major types of clusters of infected cells seen at 5--40 days after infection: (i) horizontal basal cells (HBCs); (ii) variable numbers of globose basal cells (GBCs), and immature and mature sensory neurons. Olfactory nerve lesion increased the frequency of the globose/sensory neuron clusters, as well as the number of cells/cluster, but did not change the number of HBC clusters or cells/cluster. No clusters contained sustentacular cells. These data indicate that, at least in young rats: (i) HBCs are not precursors of olfactory neurons; (ii) there is a lineage path from GBCs to mature neurons; and (iii) sustentacular cells arise from a separate lineage.

Alkaline Phosphatase↗

Are there structural and functional modules in the vertebrate olfactory bulb?

A number of different recording methods have shown that odorants elicit patterns of neuronal activity widely distributed across cells of the olfactory receptor epithelium, olfactory bulb, and piriform cortex in the vertebrate olfactory system. These findings suggest that the physicochemical properties of odorant molecules are processed by distributed coding mechanisms activated in parallel in olfactory circuits in order to characterize a single, "monomolecular" odorant. These findings also suggest that the response patterns seen at higher levels are set up by differential responses in peripheral receptor cells of the olfactory epithelium. One requirement for understanding the details of this proposed encoding scheme is correlation of odor-generated patterns with the components of these circuits. In this paper, results from 2-deoxyglucose and voltage-sensitive dye studies suggest that certain components of these responses may relate to patterns established in reproducibly identifiable aggregates of bulbar cells. These findings are consistent with previous observations suggesting that columnar groups of periglomerular, mitral/tufted and granule cells, oriented perpendicular to the laminae of the bulb, are functionally related to one another. Such cell groups or modules, when activated in parallel, could serve as building block components of the complete ensemble response. According to this hypothesis, different sets of such modules would be activated with different odorant stimuli and modules could be shared to the degree to which the physicochemical properties of the different stimuli overlap.

Animals↗

GABAA and glutamate receptor involvement in dendrodendritic synaptic interactions from salamander olfactory bulb.

1. Whole-cell patch clamp and optical recording techniques were applied to the same in vitro salamander olfactory bulb preparations to study the postsynaptic responses of single mitral/tufted cells in the context of the surrounding neural activity in which they are embedded. Mitral/tufted cells were identified by intracellular filling with biocytin. 2. Single mitral/tufted cells were under a tonic GABAA receptor-mediated inhibitory influence as revealed by the recording of bicuculline methiodide (BMI)/picrotoxin-sensitive inhibitory postsynaptic currents (IPSCs) in symmetrical chloride conditions at a holding potential of -70 mV. Depolarizing voltage steps (100 ms) applied to single cells or electrical stimulation of the olfactory nerve or medial olfactory tract evoked a prolonged increase in the frequency of GABAergic IPSCs. 3. The frequency of spontaneous and driven IPSCs was reduced with application of the glutamate receptor antagonists 6-cyano-2,3-dihydroxy-7-nitro-quionoxaline (CNQX) or 2-amino-5-phosphonopentanoic acid (AP5) whereas olfactory nerve- or medial olfactory tract-driven IPSC frequency was enhanced with removal of bathing Mg2+, indicating that GABAergic interneurones were driven by mitral/tufted cells at both non-NMDA and NMDA receptors. 4. Olfactory nerve or medial olfactory tract stimulation evoked widely distributed changes in fluorescence in preparations stained with the voltage-sensitive dye RH414. The optical response predominantly consisted of a decrease in fluorescence, indicative of depolarization. The presence of the dye did not obviously affect mitral/tufted cell postsynaptic responses. 5. BMI enhanced the amplitude and duration of optical signals related to depolarization within the bulb and in regions central to the bulb. In the presence of BMI, depolarizing activity appeared to spread hundreds of micrometres into regions of the bulb not activated in control conditions showing explicitly that GABAA receptors in the bulb participate in lateral inhibition. 6. CNQX and AP5 attenuated the optical signals within the bulb supporting the contention that in these conditions, optical signals arise mainly from granule cell dendritic activity. Furthermore, AP5 or removal of bath Mg2+ reduced or enlarged the spatial distribution of activity respectively, suggesting that in some cases the NMDA receptor may be involved in generating or stabilizing spatial patterns of activity. 7. It is concluded that in the salamander olfactory bulb, both GABAA- and glutamate receptor-mediated synaptic transmission shape the different temporal and spatial patterns of neural activity associated with olfactory coding.

2-Amino-5-phosphonovalerate↗

Intracellular injection of vital dyes into single cells in the salamander olfactory epithelium.

Intracellular vital dye injection was used to examine the morphology of single sustentacular and receptor cells and the developmental fate of individual basal cells in the olfactory epithelium of the tiger salamander. In acute experiments, Lucifer yellow injections were used to identify single basal, receptor or sustentacular cells on the basis of their overall morphology. Dye-coupling between a number of the different epithelial cells was observed. Progeny of basal cells were examined by following labeled cells for up to 2 weeks using intracellular injection of rhodamine-labeled dextran. These experiments indicate that some olfactory epithelial cells are dye-coupled and that dye-filled basal cells can undergo division and migration.

Ambystoma↗

Emergent properties of odor information coding in a representational model of the salamander olfactory bulb.

In the salamander olfactory bulb, mitral output cells exhibit a variety of responses to electrical and odor stimulation, but the cellular interactions within the bulb that give rise to these responses are not completely understood. We have developed a computer model to investigate whether available data are sufficient for formulating a simulated bulb circuit that can generate realistic mitral cell output. A set of coupled difference equations incorporating mathematical descriptions of anatomical and physiological data was used to calculate changes in membrane potentials of olfactory bulb neurons over time. Model mitral cells showed responses to simple orthodromic and antidromic electrical stimuli that were similar to salamander intracellular responses. Without changing the parameters of the equations, simulated odor stimuli were applied that elicited complex patterns of mitral depolarization, spike activation, and hyperpolarization that emerged from the interactions among the numerous elements in the model. As with the electrical stimuli, model mitral responses to odor were also strikingly similar to those of real mitral cells. As an initial test of how different circuit components contribute to the responses, the lateral interactions between mitral cells and bulbar interneurons were manipulated. Tests with reduced lateral interactions and other tests with no inhibitory synaptic connections both produced mitral cell outputs that were uncharacteristic of salamander recordings. The similarity of the model's output to the complex properties of salamander single-cell recordings suggests that several critical features of the bulb circuit responsible for shaping mitral cell responsivity have been captured.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambystoma↗

Contributions of topography and parallel processing to odor coding in the vertebrate olfactory pathway.

Odor information appears to be encoded by activity distributed across many neurons at each level in the olfactory pathway. Thus olfactory circuits function as parallel distributed processors. New methods for observing distributed activity in such systems permit computer simulations to be constructed that are constrained by patterns of activity observed in the real system. Analysis of the system using a combination of physiological measurements and computational approaches might elucidate the principles by which odors are discriminated.

Animals↗

Pathologic changes in olfactory neurons in Alzheimer's disease.

Olfactory deficits and degenerative changes in central olfactory pathways are prominent in patients with Alzheimer's disease (AD). We hypothesized that peripheral olfactory neurons that reside in the nasal epithelium would show degenerative changes similar to the characteristic pathologic features of AD brain. Immunohistochemical studies of nasal tissue taken at autopsy reveal extensive degeneration in the sensory epithelium as well as abnormal neurites that share immunoreactive epitopes with dystrophic neurites and neurofibrillary tangles of the AD brain. The neuritic masses are stained with well-characterized monoclonal antibodies that do not normally stain olfactory neurons but which are very reactive with dystrophic neuritic structures and neurofibrillary tangles in AD brain. These include antibodies to phosphorylated and nonphosphorylated neurofilament subunits, tau, and also ALZ50, which is characteristically reactive with AD but not with normal brains. Such changes are present in 81% of AD patients. Similar accumulations of ectopic neurites are found in the olfactory epithelium of about 22% of non-demented patients. Preliminary statistical analysis fails to reveal any age-linked association. It has been proposed that the aged monkey is a good model for AD inasmuch as amyloid accumulations similar to those of humans are found in monkey brain. We examined a series of 13 rhesus monkeys, including aged animals with behavioral deficits. Although the olfactory epithelium was very similar to that of humans, no abnormal olfactory structures were observed. Aged rhesus monkeys do not appear to be a good model for the neuritic abnormalities of AD.

Alzheimer Disease↗

Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography.

There are at least two basal cell populations in the olfactory epithelium that could give rise to olfactory neurons during development, in the normal adult, and after experimentally induced receptor cell death. These populations have been subdivided as horizontal (HBC) and globose (GBC) basal cells on the basis of morphological criteria and by staining with antibodies against cytokeratin. HBCs are positive for cytokeratin while GBCs are negative. We have studied which cell type is induced to divide during receptor cell regeneration stimulated by olfactory bulbectomy using a combination of immunocytochemistry and autoradiography. By examining which population increases its labeling index with 3H-thymidine (3H-TdR) at various times after bulbectomy, it is shown that there is an increase in 3H-TdR uptake in the cytokeratin-negative GBCs with no change in the cytokeratin-positive HBCs. This suggests that the GBCs are specifically induced to divide in response to cues that accompany receptor cell death, and it is thus concluded that these cells are among the precursors of new olfactory receptor neurons.

Animals↗

Day-night variation in prepro vasoactive intestinal peptide/peptide histidine isoleucine mRNA within the rat suprachiasmatic nucleus.

Neurons within the suprachiasmatic nuclei of the hypothalamus (SCN) appear to function as a circadian clock that controls the timing of many physiological systems. The SCN contain several chemically distinct neuronal subpopulations, including a large group of interneurons within the ventrolateral SCN that exhibit co-localizable immunoreactivity for both vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI). The purpose of the present study was to determine whether VIP/PHI neurons within the rat SCN exhibit rhythmicity in the cellular levels of the messenger RNA encoding the precursor from which both VIP and PHI are derived. Using both quantitative in situ and solution hybridization prepro-VIP/PHI mRNA levels early in the dark phase were demonstrated to be significantly higher than those 5 h after the onset of the daily light period. Since no statistically reliable (P greater than 0.05) day-night variation was observed in the levels of prepro-VIP/PHI mRNA within cortex, these data suggest that the rhythmicity in prepro-VIP/PHI mRNA is an intrinsic property of VIP/PHI-containing SCN neurons, or rhythmically driven by local synaptic events within the SCN.

Animals↗

Computer-assisted three-dimensional reconstructions of [14C]-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot.

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by [14C]-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1, were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: 1) Three-dimensional volume images were color-coded to represent different levels of functional activity. 2) On the reconstructed volumes, "virtual" sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. 3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.

Animals↗

Pathological changes in olfactory neurons in patients with Alzheimer's disease.

Alzheimer's disease is a central nervous system disorder characterized by the presence of neurofibrillary tangles, neuritic plaques and dystrophic neurites in susceptible areas of the brain. Investigation of the mechanism and development of the disease has been hampered by the lack of an animal model and the inaccessibility of neural tissue during the illness. Deficits in odour detection and discrimination are among the signs of Alzheimer's and previous anatomical studies suggest that olfactory pathways may be involved early in the illness. Neurons in the olfactory epithelium, which are of central origin, are relatively accessible for biopsy and could be used as a source of living nerve cells for the study of Alzheimer's disease if they can be shown to have characteristics of this disease. As these neurons have the unusual property of arising from stem cells throughout the life of the organism, they are good candidates for the development of cell cultures or cell lines which may express the disorder from living patients. We report here that nasal epithelium tissue taken at autopsy shows unique pathological changes in morphology, distribution and immunoreactivity of neuronal structures in patients with Alzheimer's disease.

Adult↗

Patterns of intracellular potentials in salamander mitral/tufted cells in response to odor stimulation.

1. Changes in membrane potential and temporal patterns of spikes were analyzed in 30 output cells in the salamander olfactory bulb in response to stimulation with 1-s pulses of the odorants isoamyl acetate, cineole, and camphor. The odor responses were more complex than responses to electrical stimulation of the olfactory nerve or olfactory tracts, with which they were compared. Most began with hyperpolarization and contained prolonged hyperpolarizing and depolarizing potentials that appeared to be compound postsynaptic potentials. These potentials were related to periods of spike inhibition and excitation. The temporal patterns of the responses resembled S-type (for suppression) and E-type (for excitation) patterns described previously in extracellular-unit studies. 2. In single cells, graded but nonmonotonic changes in the responses were observed with increases in the odor concentration from 10(-3) to 10(-1) vapor-phase saturation. Abrupt changes from one category of temporal response pattern to another were generally not observed in response to different concentrations of a single odorant but were frequently observed when the stimulus was changed from one odorant to another. 3. In S-type patterns, the first event was always membrane hyperpolarization and spike inhibition, regardless of the odor concentration. At all concentrations, simple S-type responses were observed in which a single period of hyperpolarization and inhibition lasted several seconds. At moderate to high concentrations, complex S-type responses were observed in which a period of excitation followed an initial period of hyperpolarization and inhibition. In these responses, spikes were often elicited near the termination of the odor pulse, occasionally as early as 300-400 ms after pulse onset. A prolonged period of inhibition followed the period of excitation. 4. In E-type patterns, the first event depended on the odor concentration. At all concentrations, complex responses were observed in which a period of excitation occurred with short latency, followed by a period of inhibition. At low to moderate concentrations, a brief initial period of hyperpolarization preceded the excitation. This initial period of hyperpolarization was always shorter than those in complex S-type responses to equivalent concentrations. However, the range of spike latencies overlapped that of S-type responses to high concentrations. With increasing odor concentration, spike latencies in the E-type responses decreased relative to the onset and peak of the initial hyperpolarization. At high concentrations. spikes were frequently elicited preceding a single period of hyperpolarization and inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Metabolic mapping of 2-deoxyglucose uptake in the rat piriform cortex using computerized image processing.

Using a computerized image processing method, the metabolic activity of the unfolded molecular and pyramidal layers of the piriform cortex was studied in rats during odorous stimulation. Animals were either intact or had sustained a bilateral transection of the lateral olfactory tract. 2-DG labelling was observed in corresponding areas across these two layers. No spatial pattern of 2-DG uptake could be seen in correlation with the odorant quality. These results are discussed with respect to the known anatomical and functional properties of the piriform cortex.

Animals↗

Real-time imaging of evoked activity in local circuits of the salamander olfactory bulb.

The encoding of olfactory information in the central nervous system (CNS) depends on spatially distributed patterns of activity generated simultaneously in many neuronal circuits. Optical neurophysiological recording permits analysis of neural activity non-invasively and with high spatial and temporal resolution. Here, a video method for imaging voltage-sensitive dye fluorescence in vivo is used to map neuronal activity in local circuits of the salamander olfactory bulb. The method permits the imaging of simultaneous ensemble transmembrane activity in real time. After electrical stimulation of the olfactory nerve, activity spreads centripetally from the sites of synaptic input to generate nonhomogeneous response patterns that are presumably mediated by local circuits within the bulbar layers. The results also show the overlapping temporal sequences of activation of cell groups in each layer. The method thus provides high resolution, sequential video images of the spatial and temporal progression of transmembrane events in neuronal circuits after afferent stimulation and offers the opportunity for studying ensemble events in other brain regions.

Animals↗

Responses of mitral/tufted cells to orthodromic and antidromic electrical stimulation in the olfactory bulb of the tiger salamander.

1. Responses evoked by electrical stimulation of the olfactory nerve and olfactory tracts were analyzed in 46 output cells of the salamander olfactory bulb, in vivo. Labeling of several cells with horseradish peroxidase indicated that they were mitral and/or tufted neurons. The responses contained reproducible sequences of depolarizing and hyperpolarizing potentials, which changed with increases in stimulus intensity. 2. Stimulation of the nerve with intensities subthreshold for evoking spikes in the recorded cell resulted in a small depolarization followed by a period of hyperpolarization, during which spontaneous spikes were suppressed. With suprathreshold stimulus intensities, a single spike or often a burst of spikes was evoked, followed by a complex prolonged hyperpolarization. When full spikes were blocked by injecting hyperpolarizing current through the recording electrode, an excitatory postsynaptic potential (EPSP) with two major components and sometimes a fast prepotential were observed at the beginning of the response. Amplitudes of the EPSP and hyperpolarization increased with graded increases in stimulus intensity. In tests with paired stimulus volleys, spike generation was inhibited for at least 1 s and often for several seconds during the hyperpolarization. 3. Stimulation of the tracts with intensities subthreshold for evoking spikes in the recorded cell resulted in a complex prolonged hyperpolarization. With suprathreshold stimulus intensities, a single spike was evoked, followed by a similar period of hyperpolarization. When full spikes were blocked by injecting hyperpolarizing current through the recording electrode, a small antidromic spike, presumably generated in the axon or initial segment, was often observed. Amplitude of the hyperpolarization increased with graded increases in stimulus intensity. In tests with paired volleys, generation of a full antidromic spike was inhibited for a period that usually began 20-30 ms, following the spike evoked by the conditioning stimulus and lasted 100-500 ms. Full antidromic spikes were evoked prior to the period of inhibition and small antidromic spikes were evoked during the period. 4. The mean latencies of single evoked spikes or the first spikes of bursts decreased from 22 to 17 ms with increases in the intensity of nerve stimulation and from 7 to 6 ms with increases in the intensity of tract stimulation. Only decreases in orthodromic latency were significant at P less than or equal to 0.05, as determined by one-sided t tests between the means of responses subdivided according to response pattern and relative stimulus intensity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗