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S J Fung

Publications and source records attributed to S J Fung.

At least 19 recordsLinked to original sources
PubMed2005

Metallothionein biology in the ageing and neurodegenerative brain.

In recent years metallothionein (MT) biology has moved from investigation of its ability to protect against environmental heavy metals to a wider appreciation of its role in responding to cellular stress, whether as a consequence of normal function, or following injury and disease. This is exemplified by recent investigation of MT in the mammalian brain where plausible roles for MT action have been described, including zinc metabolism, free radical scavenging, and protection and regeneration following neurological injury. Along with other laboratories we have used several models of central nervous system (CNS) injury to investigate possible parallels between injury-dependent changes in MT expression and those observed in the ageing and/or degenerating brain. Therefore, this brief review aims to summarise existing information on MT expression during CNS ageing, and to examine the possible involvement of this protein in the course of human neurodegenerative disease, as exemplified by Alzheimer's disease.

Aging↗
PubMed2001

Hypocretin (orexin) input to trigeminal and hypoglossal motoneurons in the cat: a double-labeling immunohistochemical study.

In trigeminal and hypoglossal motor nuclei of adult cats, hypocretin immunoreactive fiber varicosities were observed in apposition to retrogradely labeled motoneuron somata and dendrites. Among those lateral hypothalamus neurons that project to the hypoglossal nucleus some were determined to be hypocretin immunoreactive and were located amongst the single-labeled hypocretinergic neurons. These data suggest that hypocretin may play a role in the synaptic control of these motoneurons.

Animals↗
PubMed2000

Changes in electrophysiological properties of cat hypoglossal motoneurons during carbachol-induced motor inhibition.

The control of hypoglossal motoneurons during sleep is important from a basic science perspective as well as to understand the bases for pharyngeal occlusion which results in the obstructive sleep apnea syndrome. In the present work, we used intracellular recording techniques to determine changes in membrane properties in adult cats in which atonia was produced by the injection of carbachol into the pontine tegmentum (AS-carbachol). During AS-carbachol, 86% of the recorded hypoglossal motoneurons were found to be postsynaptically inhibited on the basis of analyses of their electrical properties; the electrical properties of the remaining 14% were similar to motoneurons recorded during control conditions. Those cells that exhibited changes in their electrical properties during AS-carbachol also displayed large-amplitude inhibitory synaptic potentials. Following sciatic nerve stimulation, hypoglossal motoneurons which responded with a depolarizing potential during control conditions exhibited a hyperpolarizing potential during AS-carbachol. Both spontaneous and evoked inhibitory potentials recorded during AS-carbachol were comparable to those that have been previously observed in trigeminal and spinal cord motoneurons under similar experimental conditions as well as during naturally occurring active sleep. Calculations based on modeling the changes that we found in input resistance and membrane time constant with a three-compartment neuron model suggest that shunts are present in all three compartments of the hypoglossal motoneuron model. Taken together, these data indicate that postsynaptic inhibitory drives are widely distributed on the soma-dendritic tree of hypoglossal motoneurons during AS-carbachol. These postsynaptic inhibitory actions are likely to be involved in the pathophysiology of obstructive sleep apnea.

Animals↗
PubMed1999

Hypoglossal motoneurons are postsynaptically inhibited during carbachol-induced rapid eye movement sleep.

The obstructive sleep apnea syndrome is characterized by the occurrence of cyclic snoring and frequent apneic episodes during sleep, with consequent hypoxia and hypercapnia. Obstructive sleep apnea syndrome is associated with excess daytime sleepiness, depression, and an increased incidence of ischemic cardiopathy, cardiac arrhythmias, systemic hypertension and brain infarction. Hypoglossal motoneurons, which innervate extrinsic and intrinsic muscles of the tongue, play a key role in maintaining the patency of the upper airway and in the pathophysiology of obstructive sleep apnea syndrome. Based on data obtained by using extracellular recording techniques, there is a consensus that hypoglossal motoneurons cease to discharge during rapid eye movement sleep, because they are disfacilitated. Since other somatic motoneurons are known to be postsynaptically inhibited during rapid eye movement sleep, we sought to determine, by the use of intracellular recording techniques during cholinergically induced rapid eye movement sleep, whether postsynaptic inhibitory mechanisms act on hypoglossal motoneurons. We found that, during this state, a powerful glycinergic premotor inhibitory system acts to suppress hypoglossal motoneurons. This finding opens new avenues for the treatment of obstructive sleep apnea syndrome, and provides a foundation to explore the neural and pharmacological control of respiration-related motoneurons during rapid eye movement sleep.

Action Potentials↗
PubMed1998

Cholinergic neurons of the dorsal pontine tegmentum projecting to the cerebellar vermal cortex of the kitten.

Although the whole cerebellar cortex receives cholinergic afferents, the source of origin of this projection has been clarified only for some corticocerebellar regions. Experiments were performed in kittens to investigate whether the two major cholinergic groups of the brainstem, the pedunculopontine (PPT) and laterodorsal tegmental nuclei (LDT), contribute to the cholinergic innervation of the cerebellar cortex, in particular the vermal cortex. Tegmento-cerebellar projecting neurons were identified by injecting the retrograde tracer rhodamine-labeled latex microspheres in the lobules V to VII of the cerebellar vermis. Subsequently, some of these tegmento-cerebellar neurons were demonstrated to be cholinergic by using the immunohistochemical technique for choline acetyltransferase (ChAT). Only a small portion of the ChAT-positive tegmental neurons projected to the cerebellar vermis. However, among the whole population of the retrogradely labeled tegmental neurons about one third were cholinergic. These cholinergic tegmento-cerebellar neurons were located in the PPT, LDT, and also within the locus coeruleus (LC) complex, where noradrenergic neurons predominate. Since the LC complex sends noradrenergic afferents to the cerebellar cortex, it appears that the dorsal pontine area contributes to the tegmento-cerebellar projections not only with noradrenergic but also with cholinergic afferents. The physiological significance of this cholinergic projection to the cerebellar cortex has been discussed.

Animals↗
PubMed1995

Localization of glutamatergic neurons in the dorsolateral pontine tegmentum projecting to the spinal cord of the cat with a proposed role of glutamate on lumbar motoneuron activity.

Glutamate is considered to be a major excitatory neurotransmitter in the central nervous system. The presence of glutamate-like immunoreactive neurons in the rodent locus coeruleus has been reported previously. In this study we used both immunohistochemical and electrophysiological techniques to answer two major questions: (1) Is there any glutamate-like immunoreactivity in the catecholaminergic coeruleospinal system of the cat? (2) What is the physiological role, if any, of glutamate in descending locus coeruleus control of spinal motoneurons? Following injections of rhodamine-labeled latex microspheres or Fast Blue into the seventh lumbar segment of the spinal cord of the cat, retrogradely labeled cells were found throughout the rostrocaudal extent of the dorsolateral pontine tegmentum. They were primarily observed in the nucleus locus coeruleus and the Kolliker-Fuse nucleus. Some labeled cells were also present in the nucleus subcoeruleus and, to a lesser extent, in the parabrachial nuclei. Data from immunohistochemical studies indicate that 86% of all dorsolateral pontine tegmentum neurons that project to the spinal cord contain glutamate-like immunoreactivity, and 77% co-contain both glutamate- and tyrosine hydroxylase-like immunoreactivity. Electrical stimulation (four pulses of 500 microseconds duration at 500 Hz; intensity = 50-200 microA) of the locus coeruleus, in decerebrate cats, consistently induced lumbar motoneuron discharges recordable ipsilaterally as ventral root responses. These motoneuronal responses were reversibly antagonized following chemical inactivation of noradrenergic locus coeruleus neurons by local infusion of the alpha 2-adrenergic agonist clonidine, suggesting the locus coeruleus neurons to be the main source of evoked ventral root responses. Additionally, the evoked ventral root responses were reversibly reduced by 34.20 +/- 4.45% (mean +/- S.E.M.) upon intraspinal injections of the non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into the ventral horn of seventh lumbar spinal cord segment (three to four injections, 20 nmol in 0.2 microliter of 0.1 M Tris-buffered saline for each injection). Similar volumes of vehicle injections had no significant effect on the locus coeruleus-evoked ventral root responses. These ventral root responses were also partially blocked (62.30 +/- 11.76%) by intravenous administration of the alpha 1-adrenergic receptor antagonist prazosin (20 micrograms/kg). In the light of several anatomical reports of noradrenergic and glutamatergic terminals in close contact with spinal motoneurons, our present findings suggest that the locus coeruleus-evoked ventral root response probably involves the synaptic release of both norepinephrine and glutamate onto lumbar motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Anatomical evidence for the presence of glutamate or enkephalin in noradrenergic projection neurons of the locus coeruleus.

This paper reviews the anatomical evidence for the presence of glutamate (GLU) in noradrenergic neurons of the nucleus locus coeruleus (LC) and adjacent nuclei in the dorsolateral pontine tegmentum (DLPT) that project to the spinal cord, cerebellum, or cerebral cortex. Additionally, the evidence for the existence of methionine-enkephalin (ENK) in noradrenergic neurons of the DLPT that project to the spinal cord of the cat is reviewed. In these studies, we have combined the retrograde transport of either Fast Blue (FB), rhodamine labeled latex microspheres (MS), or rhodamine labeled dextran and indirect immunofluorescence histochemistry to determine whether the neurons that contain tyrosine hydroxylase (TH) and project to these terminal fields also contain GLU or ENK. The neurons of the cat that project to the spinal cord, cerebellum, and neocortex were observed in the nucleus LC and Kölliker-Fuse (KF) nucleus. They were also present, to a lesser extent, in the nucleus subcoeruleus (SC) and nuclei parabrachialis medialis (PBM) and lateralis (PBL). In the rat the majority of the neurons that project to the neocortex and hippocampus were located in the nucleus LC. Our data revealed a major proportion of these neurons to be immunostained for both GLU and TH (cat, rat), or ENK and TH (cat). Functional implications of such colocalized neurochemicals within individual LC projection neurons are discussed.

Animals↗
PubMed1994

Temporal regulation of the IgE-dependent 1,2-diacylglycerol production by tyrosine kinase activation in a rat (RBL 2H3) mast-cell line.

We explored the possible role of tyrosine kinases in the IgE-dependent regulation of 1,2-diacylglycerol (DAG) production in RBL 2H3 cells. When triggered via their high-affinity IgE receptors (Fc epsilon RI), there was a rapid phosphorylation of tyrosine residues on a number of proteins. The phosphorylation of these proteins and ultimately histamine release were inhibited in a concentration-dependent manner by the tyrosine kinase inhibitor, tyrphostin. In cells labelled with [3H]myristic acid, we observed a characteristic biphasic increase in [3H]DAG production. In the presence of tyrosine kinase inhibitor, the initial increase in DAG was still observed, but the secondary increase, which was dependent on phosphatidylcholine-specific phospholipase D (PC-PLD) activation, was completely abolished. Tyrphostin significantly inhibited IgE-dependent activation of PC-PLD, suggesting that PC-PLD activation was regulated by tyrosine phosphorylation. Furthermore, when proteins from RBL 2H3 cells were immunoprecipitated with an anti-phosphotyrosine antibody, PC-PLD activity was recovered from the immunoprecipitated fraction. These results demonstrate that the secondary, but not the initial, phase of 1,2-DAG production in response to Fc epsilon RI aggregation is regulated by the initial activation of tyrosine kinases and that PC-PLD may be regulated directly by this mechanism.

Animals↗
PubMed1994

Existence of glutamate in noradrenergic locus coeruleus neurons of rodents.

This study distinguished three types of immunolabeled neurons in nucleus locus coeruleus (LC) of the rat and mouse: cells single labeled either for tyrosine hydroxylase-like immunoreactivity (TH-LI) or glutamate (Glu)-LI, and those double labeled for both antigens. Although the double labeled neurons tend to be located in the middle and ventral thirds of the rat LC nucleus, throughout its rostrocaudal extent, such feature was not apparent in the mouse. Quantitatively a majority of neurons cocontaining TH- and Glu-LI were commonly observed in the rat (62%) and mouse (77%) LC. Additional studies utilizing the combined retrograde and immunohistochemical labeling revealed that such a high incidence of coexistence of the TH- and Glu-LI was also represented by coeruleocortical neurons in the rat (69% and 75% of all ipsilateral and contralateral projection cells, respectively). A possible role of coeruleocortical neurons involvement in Glu- and norepinephrine-mediated target neuron dysfunction is discussed.

Animals↗
PubMed1994

Bulbospinal neurons of the cat that co-contain serotonin and methionine enkephalin.

The present study utilizes a combined retrograde transport of Fast Blue (or rhodamine-labeled latex microspheres) and simultaneous immunofluorescence technique to demonstrate directly the coexistence of serotonin and methionine enkephalin in bulbospinal neurons of the cat. The bulbospinal neurons that immunostained for both serotonin and enkephalin were observed, without any distinct somatotopic organization, in the nuclei raphe pallidus, obscurus and magnus. They were also observed in the nucleus reticularis magnocellularis and the ventrolateral medulla (cell group B1/3). Among the bulbospinal neurons encountered within individual 5-HT-rich medullary nuclei, high proportions of these neurons co-containing serotonin and methionine enkephalin were evidenced in the nucleus raphe obscurus (64%) and nucleus raphe pallidus (56%), less so in cell group B1/3 (41%), nucleus raphe magnus (39%), and the nucleus reticularis magnocellularis (29%). Physiological significance of such a morphological substrate is discussed.

Amidines↗
PubMed1993

Immunohistochemical localization of glutamate-containing neurons in the lateral reticular nucleus projecting to the cerebellar vermis in the kitten.

The lateral reticular nucleus (LRN) and afferents to the cerebellum are known to contain glutamate-like immunoreactive (Glu-LI) neurons and axons, respectively. However, such a direct link between the Glu-LI LRN neurons and the cerebellar vermal cortex has not been identified. In this study we have combined the retrograde transport of rhodamine labeled latex microspheres and immunofluorescence histochemistry to determine the locations of Glu-LI neurons of the kitten reticulocerebellar system. Following microsphere injections into the cerebellar vermis (lobules V-VII), retrogradely labeled neurons were encountered throughout the rostrocaudal extent of the LRN. More than 60% (n = 3 kittens) of these retrogradely labeled neurons were immunostained for Glu-like immunoreactivity. Our observations of the Glu-like immunoreactivity in a majority of the reticulocerebellar neurons suggest that Glu in these neurons may participate in LRN's control of target neuron activities in the cerebellar vermis of kittens.

Animals↗
PubMed1993

Opioid action on spinal cord reflexes due to dorsolateral pontine tegmentum stimulation.

Electrical stimulation of the dorsolateral pontine tegmentum (DLPT) produces phasic facilitatory and inhibitory actions on the lumbar spinal monosynaptic reflexes (MSRs) of both flexor and extensor muscle nerves in the decerebrate cat. Naloxone, an opioid receptor antagonist, given intravenously or intraspinally enhanced the DLPT-induced potentiation of MSRs in most of the reflexes studied. However, systemic naloxone had no significant effect on the unconditioned MSR of the spinal cord. Intraspinal microinjections of naloxone significantly attenuated the DLPT-induced inhibition of MSRs of both flexors and extensors, similar to the action of systemic injection of naloxone, indicating a direct opioid action at the spinal ventral horn level upon DLPT stimulation. Results of the present experiment further support the anatomical finding that there are pontospinal enkephalinergic pathways in the cat, and indicate that these descending pathways modulate spinal motor outflow.

Animals↗
PubMed1992

Application of compiled BASIC in developing software for collection and analysis of neuronal firing frequency data.

Two programs are described which use an IBM-AT compatible personal computer, equipped with an analog-to-digital converter, to collect and analyze electrophysiological data. The first program is used to determine neuron firing rates during intracellular experiments and to save these results on disk. The second program is used to perform off-line analysis of the frequency data. Both programs are written entirely in the well known BASIC language and the Microsoft QuickBASIC compiler is employed for their use. All of the necessary hardware can be purchased commercially. In this paper emphasis is placed on the strategies and limitations involved when this high-level language is applied to tasks often needed in data acquisition and analysis. Both on- and off-line collection schemes are considered. This software is available from the authors.

Animals↗
PubMed1992

Effects of temperature and analyte application technique on neuron-based chemical sensing.

Results are presented which enhance the field of neuron-based sensing by providing insight on the effects of operating temperature and analyte application technique (pulse versus back-mixed) on sensing properties. In these studies, serotonin sensing attributes of giant visceral neurons VV1 and VV2 from the pond snail Lymnea stagnalis were measured. Experiments using a rapid fluid-exchange system reveal a concentration-dependent increase in maximum firing frequency similar to that reported earlier for a slow well-mixed application. With a rapid application, however, the maximum firing frequency is reached more quickly, and there is less cell-to-cell variability in both the maximum response and sensitivity. Given an application technique, an increase in temperature causes an increase in sensitivity and maximum firing frequency, as well as a decrease in the time required for the response to return to baseline following removal of the analyte. To provide insights on the kinetics of the serotonin-induced response, the effects of temperature and concentration on the rates of activation, recovery and desensitization were examined in detail. In general, it was found that an increase in temperature increases the rates of activation and desensitization, while the effects on recovery were not apparent. In addition, both the rates of activation and desensitization have a direct dependence on concentration while the rate of recovery has an inverse dependence.

Action Potentials↗
PubMed1991

Optimization of glass microelectrode properties by response surface methodology.

Glass microelectrodes filled with electrolyte solutions are standard tools for electrophysiological studies. However, for any given application, there are limitations to the properties of the microelectrode, such as impedance and shank length, that can yield satisfactory results. The trial and error approach in pulling electrodes with the desired properties can be time consuming. The use of a response surface procedure which allows the experimenter to change more than one factor at a time and therefore determine the desired puller condition more efficiently is demonstrated. Also, design improvements for the World Precision Instrument, Model PUL-1, Microelectrode puller, used in this study are suggested.

Animals↗
PubMed1991

Pontospinal transmitters and their distribution.

The dorsolateral pontine tegmentum of the cat is known to contain a large population of catecholaminergic neurons. Additionally, several studies have also shown the presence of other neurochemicals (acetylcholine, enkephalin, neuropeptide Y, serotonin, somatostatin and substance P). In this study, we have employed retrograde transport of horseradish peroxidase in combination with immunocytochemistry to determine the locations of pontospinal neurons which contain catecholamine, enkephalin, neuropeptide Y, and serotonin. Furthermore, we have combined the retrograde transport of Fast Blue and immunofluorescence histochemistry to determine whether enkephalin-containing neurons are catecholaminergic. All pontospinal neurons, irrespective of the neurochemical content, were observed in the ventral and lateral parts of the dorsolateral pontine tegmentum at coronal levels P1.8-P4.0. These neurons were located in the nuclei locus coeruleus alpha and subcoeruleus and the Kölliker-Fuse nucleus. A high concentration of these neurons was evident in the Kölliker-Fuse nucleus when compared to the nuclei locus coeruleus alpha and subcoeruleus. Quantitative data have revealed that enkephalin is contained in a large proportion of the pontospinal catecholaminergic neurons (75%). The observations suggest that catecholaminergic neurons may contain one or more putative peptide neurotransmitters.

Animals↗
PubMed1991

Norepinephrine effects on spinal motoneurons.

Intracellular recordings from cat spinal motoneurons in situ demonstrated that microiontophoretic application of NE with low-intensity ejection currents produces a slowly developing, small-amplitude depolarization of the cells, in contrast to early reports of NE-induced hyperpolarization. This depolarization was associated with an increase in excitability of the cells and a decrease in membrane conductance. These observations are consistent with the hypothesis that NE reduces potassium conductance in spinal motoneurons as has been proposed for facial motoneurons (VanderMaelen and Aghajanian, 1980) and thalamic neurons (McCormick and Prince, 1988). The time course of the facilitatory effects of NE on cat motoneuron excitability recorded intracellularly agreed very closely with the time course of NE-induced facilitation of glutamate-evoked excitability in rat spinal motoneurons recorded extracellularly. The similarity of the observations in rats and cats suggests that NE functions generally to enhance mammalian motoneuron responsiveness to excitatory input.

Action Potentials↗