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C A Greer

Publications and source records attributed to C A Greer.

At least 55 records · Page 3Linked to original sources
PubMed1991

Organization of mitochondria in olfactory bulb granule cell dendritic spines.

In contrast to dendritic spines with only postsynaptic functions, the spines of olfactory bulb granule cells subserve both pre- and postsynaptic roles. In single sections these spines were previously seen to contain mitochondria, most likely needed to provide energy for presynaptic functions, but their frequency and distribution were unknown. In order to understand the organization of mitochondria in these specialized dendritic appendages, we have studied the geometry and cytoplasmic organization of granule cell spines with computer-assisted reconstructions of serial electron micrographs. The spine heads were seen to be elliptical in shape with a single pair of reciprocal synapses on the concave face apposed to the mitral/tufted cell dendrite. Mitochondria were found localized in the spine neck as well as the spine head and often extended between the two compartments. Based on their variable distribution it seems reasonable to suggest that these mitochondria are motile and move in and out of spine compartments from the parent dendrite. Spine apparatus was apparent in most of the spines as membrane bound cisterns of smooth endoplasmic reticulum located close to mitochondria. The possible role of spine apparatus in facilitating the movement of mitochondria in the necks and heads of granule cell spines in the absence of microtubules is discussed.

Animals↗
PubMed1991

Local information processing in dendritic trees: subsets of spines in granule cells of the mammalian olfactory bulb.

The anaxonic granule cell of the olfactory bulb is believed to inhibit mitral and tufted cells through reciprocal dendrodendritic synapses. However, little is known about the detailed input-output properties of the granule cell. This study explores the functional properties of granule cells by using detailed reconstructions of Golgi-impregnated granule cells as the basis for computational models. Three Golgi-impregnated granule cells from the olfactory bulbs of C57BL/6j mice were selected for detailed analysis. Measurements were made of the diameter and length of all spine heads, spine necks, and dendritic branches. These measurements formed the basis of a compartmental model of each cell in which simulations of the spread of synaptic potentials within the dendritic tree were performed with SABER (Analogy, Inc.), a circuit analysis program. The results show that the degree of spread of synaptic potentials can define functionally related subsets of spines within the dendritic tree. The size of these subsets varies with the anatomical location of the input spine, the magnitude of the input, the time course of the input, the size of the spine neck resistance, and the activity of other spines. The data indicate that the functional organization of granule cell dendritic arbors is more complex than previously thought: between the level of the individual spine and the entire dendritic tree are several levels of subsets of spines that can mediate discrete localized inhibition onto subsets of mitral or tufted cell secondary dendrites within the external plexiform layer of the olfactory bulb.

Animals↗
PubMed1990

Region-specific consequences of PCD gene expression in the olfactory system.

These studies investigated the response of olfactory bulb juxtaglomerular dopamine neurons to the loss of mitral cells in 6-7-month-old Purkinje cell degeneration (PCD) mice. Previous studies in normal mice, with tyrosine hydroxylase (TH) enzyme as a marker, demonstrated that following peripheral olfactory afferent denervation the juxtaglomerular dopamine neurons exhibited a large reduction in TH activity and immunoreactivity. These intrinsic dopamine neurons also receive afferent input via dendrodendritic contacts with mitral cells. In contrast to the deficits produced by peripheral denervation, following mitral cell degeneration in homozygous recessive PCD mice, TH activity and immunoreactivity were unaltered as compared to normal heterozygous littermates. Moreover, TH activity in the substantia nigra also was unchanged, thus suggesting that the dopamine phenotype is resistant to the influences of the pcd gene. Despite the absence of a well-defined effect of the pcd gene on neurons bearing the TH phenotype, the expression of this mutation within the olfactory system is not limited to mitral cell degeneration. The current studies also demonstrate the absence of the anterior commissure, especially pars anterior, in homozygous recessive PCD mice at 6-7 months postnatal. Whether or not the loss of the anterior commissure is a primary effect or one that is secondary to mitral cell degeneration, this structural alteration provides evidence that the pcd gene exerts more widespread effects within the olfactory system that previously appreciated. The neuronal specificity of those effects remains apparent as indicated by the lack of change in TH expression.

Animals↗
PubMed1987

Golgi analyses of dendritic organization among denervated olfactory bulb granule cells.

In the vertebrate olfactory bulb, the primary projection neurons, mitral and tufted cells, have reciprocal dendrodendritic synapses with respective subpopulations of anaxonic interneurons called granule cells. In the neurological murine mutant Purkinje Cell Degeneration (PCD), all mitral cells are lost during early adulthood. As a consequence, a subpopulation of granule cells is deprived of both afferent input and efferent targets. The effect of this event on the morphology and sublaminar distribution of granule cells was studied with light microscopic Golgi procedures in affected homozygous recessive PCD mutants and normal heterozygous littermate controls. In the control mice, a minimum of three subpopulations were identified predominantly on the basis of the topology of apical dendrites and their spinous processes within the external plexiform layer (EPL) of the olfactory bulb: type I had dendrites extending across the full width of the EPL and a homogeneous distribution of spines; type II had dendritic arbors confined to the deeper EPL; type III had apical dendrites that arborized extensively within the superficial EPL with no arbors or spines present in the deeper EPL. Prior studies suggest that type II cells form connections with mitral cells; type III cells form connections with tufted cells; and type I cells may integrate information from both populations of projection neurons. In the mutant PCD mice, the classification of subpopulations of granule cells proved difficult due to a compression of dendritic arbors within the EPL. Dendritic processes followed a more horizontal tangent relative to the radial orientation seen in control mice. The length of dendritic branches was reduced by approximately 20% with a corresponding decrease in the number of spines. The density of spines (#/1 micron of dendrite) was constant in both controls and mutants at approximately 0.21. Truncation of the dendrites in the PCD mutants appeared to occur at terminal portions because the number of dendritic bifurcations was equal in both groups of mice. The data are discussed in terms of subpopulations of granule cells in the mouse olfactory bulb, the sublaminar organization of olfactory bulb circuits, and the capacity for survival and plasticity in the reciprocal dendrodendritic circuits mediated by the granule cell spines.

Animals↗
PubMed1987

Plasticity of dendrodendritic microcircuits following mitral cell loss in the olfactory bulb of the murine mutant Purkinje cell degeneration.

Mitral cells of the olfactory bulb typically form reciprocal dendrodendritic synapses with anaxonic interneurons, granule cells, within a sublamina of the external plexiform layer. As a result of mitral cell loss in the murine mutant Purkinjie cell degeneration (PCD), subpopulations of these granule cells are denervated. The present report examines the capacity of these denervated interneurons to form new dendrodendritic microcircuits with a second population of olfactory bulb neurons, tufted cells. Quantitative ultrastructural assessments were made of the morphology and distribution of dendrodendritic circuits in the olfactory bulbs of normal heterozygous littermates and affected homozygous recessive PCD mice following mitral cell loss. There were no apparent morphological characteristics that distinguished the reciprocal synaptic connections formed by mitral cells from those formed by tufted cells. However, the segregation of mitral cell dendrodendritic circuits in the deep sublamina of the external plexiform layer (EPL) and tufted cell circuits in the superficial sublamina provided the basis for a comparative analysis of synaptic organization following mitral cell loss. Following mitral cell loss there was a significant reduction in the area occupied by characteristic mitral cell dendrites within the deep sublamina of the EPL. A slight but nonsignificant increase in the area occupied by granule cell spines was also observed. The number of synaptic appositions involving granule cells decreased slightly, the number involving tufted cells increased significantly in the mutant mice. This indicates that many granule cell spines survive denervation and establish new reciprocal dendrodendritic synapses at available sites on tufted cells. In both the control and mutant mice the ratios of symmetrical:asymmetrical dendrodendritic synapses closely approached 1. This demonstrates that not only do the denervated spines receive new afferent input from tufted cell dendrites, but they also establish the reciprocal efferent projection. These data are discussed in terms of the sublaminar organization of dendrodendritic microcircuits in the olfactory bulb and their capacity of plasticity and reorganization following pertubation.

Animals↗
PubMed1985

High-resolution 2-deoxyglucose autoradiography in quick-frozen slabs of neonatal rat olfactory bulb.

We have used rapid freezing and freeze-substitution fixation to permit electron microscopic study of [3H]2-deoxyglucose autoradiographs. The techniques minimize diffusion of label into processing fluids and, by inference, migration of label within tissue. Slabs of olfactory bulbs from 12-day-old rats were quick-frozen after one hour of exposure to physiological olfactory stimuli. In light microscopic autoradiographs at low magnification, the neuropil of individual olfactory glomeruli appeared uniformly labeled with different levels of labeling in different glomeruli. At higher magnification, glomerular neuropil labeling consisted of small unlabeled regions surrounded by label clusters, suggesting greater deoxyglucose uptake by olfactory nerve terminals as compared with their postsynaptic dendrites. Periglomerular neurons were labeled differentially. Some microglia and glia precursor cells were heavily labeled in all bulbar laminae. The ultrastructure of cells and neuropil in all bulbar laminae was well-preserved. Cell processes and organelles could be identified in both stained sections and unstained electron microscopic autoradiographs. These experiments demonstrate the feasibility of combining quick-freezing with freeze substitution, in order to extend the resolution of studies using diffusable tracers such as 2-deoxyglucose. The results suggest that this is a promising method for assessing several controversies concerning deoxyglucose incorporation and neuronal and glial metabolism.

Animals↗
PubMed1984

Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity.

Animals↗
PubMed1983

Evidence for olfactory function in utero.

Pregnant rats received 2-[14C]deoxy-D-glucose (2DG) intravenously on the last day of gestation, and their fetuses were delivered 1 hour later by cesarean section. Fetal brains showed high 2DG uptake spread throughout the accessory olfactory bulb and little or no differential uptake in the main olfactory bulb. These findings demonstrate that functional activity occurs in the accessory olfactory bulb in utero and suggest that the accessory olfactory system may be the pathway by which fetal rats detect the odor quality of their intrauterine milieu.

Animals↗
PubMed1983

Laminar distributions of 2-deoxyglucose uptake in the rat spinal cord following electrical stimulation of the sciatic nerve.

The 2-deoxyglucose method was employed to study the functional organization of afferent axons in the dorsal horn of the rat spinal cord. Stimulation of axons in the sciatic nerve with conduction velocities greater than 17 m/s produced activity predominantly in the deep laminae of the dorsal horn. In contrast, stimulation of the entire population produced activity throughout the dorsal horn. The results are discussed in relation to the functional organization of the rat dorsal horn.

Animals↗
PubMed1983

The effect of intranasal zinc sulfate treatment on odor-mediated behavior and on odor-induced metabolic activity in the olfactory bulbs of neonatal rats.

This study describes the effect of lesions of the peripheral olfactory receptor sheet on odor-mediated behavior and on odor-induced metabolic activity in the neonatal olfactory bulb. Nine-day-old rats were treated by intranasal irrigation with a solution of 1% ZnSO4 or 5% ZnSO4 or saline. At 1 and 5 days following treatment they were tested for maternally-directed behaviors which are mediated in large part by olfactory cues. At 1 day following treatment the pups treated with ZnSO4 solutions had significant deficits in their odor-directed behavior. By 5 days however, most pups treated with 1% ZnSO4 had recovered to control levels, while the pups treated with 5% ZnSO4 continued to exhibit profound behavioral deficits. Following the behavioral testing, the pups were tested using the 2-deoxyglucose method for amyl acetate odor-induced metabolic activity in their olfactory bulbs. Control pups had large regions of high focal activity in their anterolateral and caudomedial olfactory bulbs. The 1% ZnSO4 pups had smaller foci which were confined primarily to the medial olfactory bulb. The 5% ZnSO4 pups had very little focal uptake in their olfactory bulbs. There was a clear correlation between intact olfactory nerve and glomerular layers and sites of increased functional activity. The results of this study demonstrate that there is a relationship between the degree of behavioral deficit and the extent of odor-induced functional activity in the olfactory bulb.

Animals↗
PubMed1982

Mitral cell degeneration and sensory function in the neurological mutant mouse Purkinje cell degeneration (PCD).

Selective degeneration of mitral cells, the principal relay neuron in the central olfactory pathway, is described in the mutant mouse Purkinje cell degeneration (PCD). Concomitant effects are described in adjacent layers of the olfactory bulb which suggest a reorganization of local neuronal circuits. The 2-deoxyglucose technique produced results which suggested that the topographical distribution of sensory afferent input to the bulb was not affected.

Animals↗
PubMed1982

Mapping of odor-related neuronal activity in the olfactory bulb by high-resolution 2-deoxyglucose autoradiography.

The spatial distribution of odor-induced neuronal activity in the olfactory bulb, the first relay station of the olfactory pathway, is believed to reflect important aspects of chemosensory coding. We report here the application of high-resolution 2-deoxyglucose autoradiography to the mapping of spatial patterns of metabolic activity at the level of single neurons in the olfactory bulb. It was found that glomeruli, which are synaptic complexes containing the first synaptic relay, tend to be uniformly active or inactive during odor exposure. Differential 2-deoxyglucose uptake was also observed in the somata of projection neurons (mitral cells) and interneurons (periglomerular and granule cells). This confirms and extends our previous studies in which odor-specific laminar and focal uptake patterns were revealed by the conventional x-ray film 2-deoxyglucose method due to Sokoloff and colleagues [Sokoloff, L., Reivich, M., Kennedy, C., DesRosiers, M. H., Patlak, C. S., Pettigrew, K. D., Sakurada, O. & Shinohara, M. (1977) J. Neurochem. 28, 897--916]. Based on results obtained by the two methods, it is suggested that the glomerulus as a whole serves as a functional unit of activity. The high-resolution results are interpreted in terms of the well-characterized synaptic organization of the olfactory bulb and also serve to illustrate the capability of the 2-deoxyglucose autoradiographic technique to map metabolic activity in single neurons of the vertebrate central nervous system.

Animals↗
PubMed1981

Topographical and laminar localization of 2-deoxyglucose uptake in rat olfactory bulb induced by electrical stimulation of olfactory nerves.

Experiments were carried out to examine the topographical projection of the olfactory nerves to the olfactory bulb in the rat, using the Sokoloff [14C]2-deoxyglucose (2-DG) technique. Electrical stimulation of a medially located bundle of olfactory nerves produced a discrete zone of 2-DG uptake at the rostral pole of the bulb. Increasing stimulus strength yielded a slightly larger focus at this site. In contrast, electrical stimulation of laterally situated bundles of olfactory nerves resulted in a broad zone of activity extending along the lateral wall of the bulb, and increasing stimulus intensity produced a more extensive area of uptake. Laminar analyses provided information on the relation between activity in the glomerular layer, where the olfactory nerves terminate, and activity in deeper layers. The results support previous studies of the topographical projections of the olfactory nerves to the olfactory bulb. They also support the hypothesis that odor-induced 2-DG uptake in the olfactory bulb represents activation of groups of receptors in the olfactory epithelium whose axons terminate in activated glomerular regions in the olfactory bulb.

Animals↗
PubMed1981

Localization of synaptic responses in the in vitro turtle olfactory bulb using the [14C]2-deoxyglucose method.

Studies were carried out on the in vitro turtle olfactory bulb preparation with a modification of the [14C]-2-deoxyglucose (2-DG) technique. Electrical stimulation of either the dorsal or ventral division of the olfactory nerve produced broad bands of activity, spreading across laminae, in the corresponding half of the olfactory bulb. Pretreatment of the isolated preparation in a low calcium bath eliminated focal 2-DG uptake induced by electrical stimulation of the nerve. In contrast, pretreatment with the GABAergic antagonist, bicuculline, produced a notable increase in 2-DG accumulation. These findings are discussed in the light of the topographical innervation of the olfactory bulb by the olfactory nerve as well as the known synaptic organization of the olfactory bulb and the putative neurotransmitters operative in local circuits.

Animals↗
PubMed1980

Paradoxical effects of d-amphetamine upon seizure susceptibility in 2 selectively bred lines of mice.

The ontogeny and substrates of amphetamine-induced changes in flurothyl-induced myoclonic and clonic seizure thresholds were investigated in 2 selectively bred lines of mice. The long-sleep mice exhibited dose-dependent increases in myoclonic and clonic susceptibility following amphetamine, irrespective of age. The noradrenergic agonist clonidine and the dopaminergic agonist apomorphine produced increases in susceptibility comparable to those seen with amphetamine. The short-sleep mice, however, exhibited a dichotomous myoclonic response to amphetamine that was age-dependent. Between 15 and 35 days of age amphetamine decreased seizure susceptibility whereas increases in susceptibility were noted at later ages. With the exception of 80 days, amphetamine did not affect clonic thresholds. In respect to myoclonus, clonidine persisted in producing effects similar to those seen in the long-sleep mice whereas apomorphine exhibited the same ontogenetic alteration in effect seen with amphetamine. These results confirm that the short-sleep mice might be a naturally occurring animal model of preadolescent hyperkinesis. Furthermore, the neuropharmacological tests demonstrate that the paradoxical response to amphetamine in the young short-sleep mice is mediated via a dopaminergic mechanism that must undergo dramatic change during ontogeny.

Age Factors↗
PubMed1979

Maturational changes related to dopamine in the effects of d-amphetamine, cocaine, nicotine, and strychnine on seizure susceptibility.

The effects of four neural excitants (damphetamine, cocaine, nicotine, and strychnine) on myoclonic and clonic seizure susceptibility were investigated in two age groups (30 and 120 days) of short-sleep mice. Amphetamine and cocaine decreased susceptibility to myoclonus in young mice and increased susceptibility in mature mice. These effects were attenuated by pretreatment with haloperidol, indicating mediation by a dopaminergic system. Amphetamine did not alter clonic susceptibility in either age group of mice, whereas cocaine affected clonic susceptibility and myoclonus. These effects were not attenuated by haloperidol, indicating mediation by systems other than dopamine. Nicotine decreased susceptibility to myoclonus and increased susceptibility to clonus, whereas strychnine increased susceptibility to both types of seizure. Haloperidol, however, failed to alter any of these effects. These results are consistent with our previous work which suggests that a dopaminergic mechanism in these mice undergoes marked developmental changes between 30 and 120 days of age.

Aging↗