9 results on '"Parks TN"'
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2. Functional synapse elimination in the developing avian cochlear nucleus with simultaneous reduction in cochlear nerve axon branching
- Author
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Jackson, H, primary and Parks, TN, additional
- Published
- 1982
- Full Text
- View/download PDF
3. Zinc inhibition of group I mGluR-mediated calcium homeostasis in auditory neurons.
- Author
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Zirpel L and Parks TN
- Subjects
- Animals, Chick Embryo, Electrophysiology, In Vitro Techniques, Intracellular Membranes metabolism, Nerve Endings metabolism, Neurons drug effects, Receptor, Metabotropic Glutamate 5, Substantia Innominata drug effects, Substantia Innominata metabolism, Vestibulocochlear Nerve metabolism, Zinc metabolism, Auditory Pathways metabolism, Calcium metabolism, Homeostasis drug effects, Neurons metabolism, Receptors, Metabotropic Glutamate physiology, Zinc pharmacology
- Abstract
Zinc is widely distributed in the central nervous system (CNS), it functions normally as a synaptic modulator, and it contributes to neuronal death under pathologic conditions. Zinc colocalizes with glutamate in excitatory synapses, and the presence of zinc is well characterized in the synapses of the auditory system. Since chick cochlear nucleus neurons depend upon synaptic activation of metabotropic glutamate receptors (mGluRs) for maintenance and survival, the goal of this study was to determine (1) if zinc is released from the eighth nerve calyces onto nucleus magnocellularis (NM) neurons in the chick cochlear nucleus, and, if so, (2) what effect it has on group I mGluR-mediated calcium homeostasis of these neurons. Using in vitro slices and a fluorescent dye relatively specific to vesicularized zinc, we show that zinc is indeed localized to the presynaptic calyces and is released upon nerve stimulation or KCl depolarization. Experiments employing fura-2 calcium imaging show that zinc inhibits group I mGluR release of calcium from internal stores of NM neurons and disrupts activity-dependent calcium homeostasis in a manner identical to the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine. The mGluR1-specific antagonist 7-hydroxyiminocyclopropan-[b]chromen-la-carboxylic acid ethyl ester did not affect release of calcium from stores by the nonspecific mGluR agonist aminocyclopentane dicarboxylic acid, nor did it affect activity-dependent calcium homeostasis. We conclude that zinc is present in and released from the glutamatergic eighth nerve calcyes. The presence of zinc inhibits mGluR5, a major component of calcium homeostasis of NM neurons, and plays a modulatory role in the activity-dependent, mGluR-mediated calcium homeostasis of auditory neurons.
- Published
- 2001
- Full Text
- View/download PDF
4. AMPA receptor-mediated, calcium-dependent CREB phosphorylation in a subpopulation of auditory neurons surviving activity deprivation.
- Author
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Zirpel L, Janowiak MA, Veltri CA, and Parks TN
- Subjects
- Animals, Apoptosis physiology, Calcium Signaling physiology, Calcium-Calmodulin-Dependent Protein Kinase Type 1, Calcium-Calmodulin-Dependent Protein Kinases metabolism, Chickens, Cochlear Nucleus pathology, Cochlear Nucleus physiopathology, Denervation adverse effects, Glutamic Acid metabolism, Neurons, Afferent pathology, Phosphorylation, Protein Kinases drug effects, Protein Kinases metabolism, Staurosporine pharmacology, Calcium metabolism, Cell Survival physiology, Cochlear Nucleus metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Neurons, Afferent metabolism, Receptors, AMPA metabolism, Sensory Deprivation physiology
- Abstract
Although dependence on afferent synaptic activity has been shown for central neurons in every sensory system, the mechanisms of afferent maintenance of target sensory neurons are not understood. Neurons in the cochlear nucleus (CN) require afferent activity for maintenance and survival. One of the earliest changes seen after activity deprivation is an increase in intracellular calcium that leads to the death of 30% of the neuronal population. Sixty minutes after deafferentation, the surviving neurons show increased phosphorylation of the transcription factor calcium/cAMP response element-binding protein (CREB). CREB phosphorylation in activity-deprived CN neurons is dependent on increased intracellular calcium resulting from influx through AMPA receptors and is mediated by calcium/calmodulin-dependent kinases and protein kinase A. We conclude that in CN neurons, the deafferentation-induced increase in calcium activates at least two kinase pathways that phosphorylate CREB in surviving neurons. We hypothesize that this phosphorylation results in the transcription of genes containing the calcium/cAMP response element within their promoter regions, and these genes code for proteins that allow the neurons to compensate for their hypercalcemic, activity-deprived state.
- Published
- 2000
5. Developmental changes in the subcellular localization of calretinin.
- Author
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Hack NJ, Wride MC, Charters KM, Kater SB, and Parks TN
- Subjects
- Animals, Basal Nucleus of Meynert embryology, Basal Nucleus of Meynert metabolism, Basal Nucleus of Meynert ultrastructure, Blotting, Western, Calbindin 2, Chick Embryo, Immunohistochemistry, Microscopy, Confocal, Neurons metabolism, Neurons ultrastructure, Subcellular Fractions metabolism, Nerve Tissue Proteins metabolism, S100 Calcium Binding Protein G metabolism
- Abstract
Brainstem auditory neurons in the chick nucleus magnocellularis (NM) express high levels of the neuron-specific calcium-binding protein calretinin (CR). CR has heretofore been considered a diffusible calcium buffer that is dispersed uniformly throughout the cytosol. Using high-resolution confocal microscopy and complementary biochemical analyses, we have found that during the development of NM neurons, CR changes from being expressed diffusely at low concentrations to being highly concentrated beneath the plasma membrane. This shift in CR localization occurs at the same time as the onset of spontaneous activity, synaptic transmission, and synapse refinement in NM. In the chick brainstem auditory pathway, this subcellular localization appears to occur only in NM neurons and only with respect to CR, because calmodulin remains diffusely expressed in NM. Biochemical analyses show the association of calretinin with the membrane is detergent-soluble and calcium-independent. Because these are highly active neurons with a large number of Ca2+-permeable synaptic AMPA receptors, we hypothesize that localization of CR beneath the plasma membrane is an adaptation to spatially restrict the calcium influxes.
- Published
- 2000
6. Contrasting molecular composition and channel properties of AMPA receptors on chick auditory and brainstem motor neurons.
- Author
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Ravindranathan A, Donevan SD, Sugden SG, Greig A, Rao MS, and Parks TN
- Subjects
- Animals, Auditory Pathways cytology, Blotting, Western, Brain Stem cytology, Calcium metabolism, Chick Embryo, Cobalt pharmacokinetics, Fluorescent Antibody Technique, Patch-Clamp Techniques, Protein Isoforms genetics, RNA Editing, RNA, Messenger metabolism, Receptors, AMPA antagonists & inhibitors, Receptors, AMPA genetics, Receptors, AMPA physiology, Spider Venoms pharmacology, Auditory Pathways metabolism, Brain Stem metabolism, Motor Neurons metabolism, Neurons metabolism, Receptors, AMPA metabolism
- Abstract
1. Neurons in the brainstem auditory pathway exhibit a number of specializations for transmitting signals reliably at high rates, notably synaptic AMPA receptors with very rapid kinetics. Previous work has not revealed a common structural pattern shared by the AMPA receptors of auditory neurons that could account for their distinct functional properties. 2. We have used whole-cell patch-clamp recordings, mRNA analysis, immunofluorescence, Western blots and agonist-evoked cobalt uptake to compare AMPA receptors on the first-, second- and third-order neurons in the chick ascending auditory pathway with those on brainstem motor neurons of the glossopharyngeal/vagal nucleus, which have been shown to have very slow desensitization kinetics. 3. The results indicate that the AMPA receptors of the cochlear ganglion, nucleus magnocellularis and nucleus laminaris share a number of structural and functional properties that distinguish them from the AMPA receptors of brainstem motor neurons, namely a lower relative abundance of glutamate receptor (GluR)2 transcript and much lower levels of GluR2 immunoreactivity, higher relative levels of GluR3 flop and GluR4 flop, lower relative abundance of the C-terminal splice variants GluR4c and 4d, less R/G editing of GluR2 and 3, greater permeability to calcium, predominantly inwardly rectifying I-V relationships, and greater susceptibility to block by Joro spider toxin. 4. We conclude that the AMPA receptors of auditory neurons acquire rapid kinetics from their high content of GluR3 flop and GluR4 flop subunits and their high permeability to Ca2+ from selective post-transcriptional suppression of GluR2 expression.
- Published
- 2000
- Full Text
- View/download PDF
7. Prevention of normally occurring and deafferentation-induced neuronal death in chick brainstem auditory neurons by periodic blockade of AMPA/kainate receptors.
- Author
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Solum D, Hughes D, Major MS, and Parks TN
- Subjects
- 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology, Animals, Auditory Pathways cytology, Auditory Pathways embryology, Brain Stem cytology, Brain Stem embryology, Cell Death drug effects, Cell Survival drug effects, Chick Embryo, Kinetics, Neurons cytology, Neurons drug effects, Piperazines pharmacology, Quinoxalines pharmacology, Receptors, AMPA antagonists & inhibitors, Receptors, Kainic Acid antagonists & inhibitors, Time Factors, Auditory Pathways physiology, Brain Stem physiology, Excitatory Amino Acid Antagonists pharmacology, Neurons physiology, Receptors, AMPA physiology, Receptors, Kainic Acid physiology
- Abstract
The role of glutamate receptors in regulating programmed neuronal death and deafferentation-induced neuronal death in the brainstem auditory nuclei was studied by in ovo drug administration to chick embryos. The nucleus laminaris (NL) undergoes programmed developmental cell death of 19% between embryonic day 9 (E9) and E17. The AMPA/kainate receptor antagonist CNQX, when administered at doses of 200-300 microg/d from E8 to E15, prevented programmed neuronal death in NL through at least posthatching day 8, without producing anatomical or behavioral abnormalities. 3-((RS)-2-Carboxypiperazin-4-yl)-propyl-1-phos-phonic acid, an antagonist of NMDA receptors, had no effect on normal cell death in the NL. CNQX, given from E8 to E15 or only from E8 to E10, also blocked the 33% neuronal loss in the nucleus magnocellularis (NM) that follows surgical destruction of the otocyst on E3, a procedure that deafferents NM neurons by preventing formation of the cochlear nerve. Treatment either with CNQX or the more highly selective NBQX from E8 to E10, before the onset of synaptic transmission in NM and NL, was also effective in preventing normal neuronal death in NL. Analysis of the effects of CNQX or NBQX on spontaneous embryonic motility at E10 showed that the doses effective in preventing neuronal death suppressed motility for <8 hr. We conclude that periodic blockade of AMPA/kainate receptors can protect CNS neurons against subsequent programmed cell death or deafferentation-induced death.
- Published
- 1997
8. Arylamine toxins from funnel-web spider (Agelenopsis aperta) venom antagonize N-methyl-D-aspartate receptor function in mammalian brain.
- Author
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Parks TN, Mueller AL, Artman LD, Albensi BC, Nemeth EF, Jackson H, Jasys VJ, Saccomano NA, and Volkmann RA
- Subjects
- Animals, Brain drug effects, Calcium metabolism, Cells, Cultured, Cytosol metabolism, Evoked Potentials drug effects, Glycine pharmacology, Hippocampus drug effects, Ibotenic Acid analogs & derivatives, Ibotenic Acid pharmacology, In Vitro Techniques, Kainic Acid pharmacology, Kinetics, N-Methylaspartate pharmacology, Neurons drug effects, Rats, Receptors, N-Methyl-D-Aspartate drug effects, Structure-Activity Relationship, Synapses drug effects, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Brain physiology, Cerebellum metabolism, Hippocampus physiology, Neurons metabolism, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Spider Venoms pharmacology, Synapses physiology, Synaptic Transmission drug effects
- Abstract
The venom of the North American funnel-web spider Agelenopsis aperta contains a variety of arylamine toxins (the alpha-agatoxins) that paralyze insects by blocking glutamatergic neuromuscular transmission. We have tested six synthetic alpha-agatoxins for their ability to antagonize glutamate receptor function in mammalian brain. These compounds produce, at submicromolar concentrations, noncompetitive inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated elevations in the concentration of cytosolic free calcium in cultured rat cerebellar granule neurons. In contrast, the alpha-agatoxins are relatively weak antagonists of elevations in the cytosolic free calcium concentration induced by non-NMDA receptor agonists. The alpha-agatoxins also produce reversible suppression of the NMDA receptor-mediated excitatory postsynaptic potential in rat hippocampal slices at concentrations that have little effect on the non-NMDA receptor-mediated population spike. We conclude that the alpha-agatoxins are selective and reversible noncompetitive antagonists at NMDA receptors in mammalian brain.
- Published
- 1991
9. Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-d-aspartate antagonist activity.
- Author
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Haack JA, Rivier J, Parks TN, Mena EE, Cruz LJ, and Olivera BM
- Subjects
- Amino Acid Sequence, Animals, Aspartic Acid antagonists & inhibitors, Aspartic Acid pharmacology, Benzofurans, Calcium metabolism, Cerebellum drug effects, Cerebellum metabolism, Chromatography, Gel, Conotoxins, Fluorescent Dyes, Fura-2, Intercellular Signaling Peptides and Proteins, Mass Spectrometry, Mice, Molecular Sequence Data, Mollusk Venoms chemical synthesis, Mollusk Venoms pharmacology, N-Methylaspartate, Neurons drug effects, Neurons metabolism, Peptides chemical synthesis, Peptides pharmacology, Rats, Seizures chemically induced, Sequence Homology, Nucleic Acid, Snails, 1-Carboxyglutamic Acid analysis, Aspartic Acid analogs & derivatives, Mollusk Venoms isolation & purification, Peptides isolation & purification
- Abstract
Conantokin-T, a 21-amino acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa. The amino acid sequence of the peptide was determined and verified by chemical synthesis. The peptide has 4 residues of the modified amino acid, gamma-carboxyglutamate (Gla). The sequence of the peptide is: Gly-Glu-Gla-Gla-Tyr-Gln-Lys-Met-Leu-Gla-Asn-Leu-Arg-Gla-Ala-Glu-Val-Lys- Lys-Asn-Ala-NH2. Conantokin-T inhibits N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. This observation suggests that like conantokin-G (a homologous Conus peptide with recently identified NMDA antagonist activity) conantokin-T has NMDA antagonist activity. A sequence comparison of conantokins-T and -G identifies the 4 Gla residues and the N-terminal dipeptide sequence as potential key elements for the biological activity of this peptide.
- Published
- 1990
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