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Torgny H. Svensson - One of the best experts on this subject based on the ideXlab platform.
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gaba b receptor mediated modulation of the Firing Pattern of ventral tegmental area dopamine neurons in vivo
Naunyn-schmiedebergs Archives of Pharmacology, 2002Co-Authors: Sophie Erhardt, Karima Chergui, Göran Engberg, J M Mathe, Torgny H. SvenssonAbstract:Previous work demonstrates the fundamental role of the Firing Pattern, specifically the burst Firing mode of midbrain dopamine (DA) neurons in the regulation of DA release. Spontaneous burst Firing has been shown to be dependent upon NMDA receptor activation of the DA cells. In addition to NMDA receptors, previous studies have reported that also GABAB receptors modulate the Firing Pattern of DA neurons in the substantia nigra. In the present electrophysiological study the role of GABAB receptors in the modulation of the Firing Pattern of DA neurons in the ventral tegmental area (VTA) in anaesthetised Sprague-Dawley rats was analysed. Systemic administration of the selective and potent GABAB receptor agonist baclofen dose-dependently reduced Firing rate and burst Firing in VTA DA neurons. An increase in the regularity of DA cell Firing was also observed. All these effects were effectively antagonized by administration of the selective GABAB antagonist CGP 35348 (100 mg/kg or 200 mg/kg, i.v.). Administration of CGP 35348 (400 mg/kg, i.v.) per se was associated with a long-lasting increase in burst Firing activity. The effects of systemic administration of baclofen, alone or in combination with CGP 35348, on the Firing rate were largely mimicked by local microiontophoretic application of the drugs onto the DA neurons.
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prazosin modulates the Firing Pattern of dopamine neurons in rat ventral tegmental area
European Journal of Pharmacology, 1993Co-Authors: J Grenhoff, Torgny H. SvenssonAbstract:Previous studies have indicated a noradrenergic modulation of midbrain dopamine cell activity. The effects of systemic administration of the alpha 1-adrenoceptor antagonist prazosin and the alpha 2-antagonist idazoxan on midbrain dopamine cell Firing were now studied with extracellular recording from single dopamine neurons in the ventral tegmental area of chloral hydrate-anaesthetized male rats. Prazosin (0.15-0.6 mg/kg i.v.) dose dependently decreased burst Firing and regularized the Firing Pattern of dopamine neurons, while the Firing rate was unaffected. The prazosin-induced effects were abolished by pretreatment with reserpine. Idazoxan (0.5-2.0 mg/kg i.v.) increased Firing rate and burst Firing and made the Firing Pattern less regular, probably by increasing adrenergic transmission via blockade of presynaptic alpha 2-adrenoceptors. The effects of idazoxan were blocked by prazosin. The present results indicate that noradrenergic neurons modulate the dopamine cell Firing Pattern via excitatory postsynaptic alpha 1-adrenoceptors. This mechanism might be involved in the pathogenesis and pharmacological treatment of schizophrenia.
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Tonic Activation of NMDA Receptors Causes Spontaneous Burst Discharge of Rat Midbrain Dopamine Neurons In Vivo
European Journal of Neuroscience, 1993Co-Authors: Karima Chergui, P. J. Charléty, C. F. Saunier, J. ‐l Brunet, Michele Buda, Torgny H. Svensson, Hideo Akaoka, G. ChouvetAbstract:Midbrain dopamine neurons in vivo discharge in a single-spike Firing Pattern or in a burst-Firing Pattern. Such activity in vivo strikingly contrasts with the pacemaker activity of the same dopamine neurons recorded in vitro. We have recently shown that burst activity in vivo of midbrain dopamine neurons is due to the local activation of excitatory amino acid receptors, as microapplication of the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly regularized the spontaneous Firing Pattern of these dopamine neurons. In the present study, we investigated which subtypes of excitatory amino acid receptors are involved in the burst-Firing of midbrain dopamine neurons in chloral hydrate-anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter the spontaneous burst Firing of dopamine neurons (n = 36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP-5), a specific antagonist at NMDA receptors, markedly regularized the Firing Pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest that burst-Firing of midbrain dopamine neurons in vivo results from the tonic activation of NMDA receptors by endogenous excitatory amino acids. In view of the critical dependency of catecholamine release on the discharge Pattern of source neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute a major physiological substrate in the control of the dopamine level in target areas.
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effects of dizocilpine mk 801 on rat midbrain dopamine cell activity differential actions on Firing Pattern related to anatomical localization
Journal of Neural Transmission, 1993Co-Authors: S Murase, J M Mathe, J Grenhoff, Torgny H. SvenssonAbstract:The effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) on the Firing Pattern of midbrain dopamine neurons were studied with single cell recording techniques in male albino rats anaesthetized with chloral hydrate. The extracellularly recorded electrical activity of single, identified dopamine neurons was studied with respect to Firing rate, burst Firing and regularity of Firing. MK-801 (0.01–1.0 mg/kg IV) induced different effects in different subgroups of midbrain dopamine neurons. In the substantia nigra, Firing rate was increased while the Pattern was regularized and burst Firing slightly increased. In the ventral tegmental area, Firing rate and regularity of Firing was also increased while effects on burst Firing were bidirectional. Histological inspections revealed that neurons which responded with an increase in burst Firing were mainly located in the nucleus paranigralis subdivision of the ventral tegmental area, while cells responding with a decrease were predominantly found in the nucleus parabrachialis pigmentosus subdivision. The effects of MK-801 were similar to previously described effects of phencyclidine, another non-competitive NMDA antagonist. The present effects of MK-801 might shed some light on the mechanisms involved in psychotic symptoms induced by phencyclidine and other non-competitive NMDA antagonists.
James M. Tepper - One of the best experts on this subject based on the ideXlab platform.
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pallidal control of substantia nigra dopaminergic neuron Firing Pattern and its relation to extracellular neostriatal dopamine levels
Neuroscience, 2004Co-Authors: Christian R Lee, Elizabeth D Abercrombie, James M. TepperAbstract:The Firing Patterns of dopaminergic neurons in vivo are strongly modulated by afferent input. The principal GABAergic inputs to the dopaminergic neurons of the substantia nigra originate from neurons of the neostriatum, globus pallidus and substantia nigra pars reticulata. It has previously been shown that the Firing Pattern of nigral dopaminergic neurons can be manipulated by pharmacologically induced excitation or inhibition of the globus pallidus with relatively little effect on Firing rate. We used this technique to explore the relation between the Firing Pattern of dopaminergic neurons and extracellular dopamine levels in the neostriatum in vivo. Specifically, we tested whether an increase in burst Firing in dopaminergic neurons produced by increased pallidal activity led to increased extracellular dopamine levels in the neostriatum. Single unit extracellular recording combined with simultaneous microdialysis was used to measure the Firing rates and Patterns of dopaminergic neurons and extracellular striatal dopamine levels, respectively, during bicuculline-induced excitation of the globus pallidus. Pallidal excitation resulted in a marked increase in burst Firing in dopaminergic neurons along with only a slight increase in Firing rate, but produced a significant elevation (approximately 45%) in neostriatal dopamine levels. These data suggest that afferent-induced burst Firing in dopaminergic neurons leads to an increase in extracellular dopamine levels in the neostriatum when compared with less bursty Patterns with similar overall Firing rates.
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GABAA and GABAB antagonists differentially affect the Firing Pattern of substantia nigra dopaminergic neurons in vivo
Synapse (New York N.Y.), 1999Co-Authors: Carlos A. Paladini, James M. TepperAbstract:The effects of local pressure application of the selective GABAA antago- nists, bicuculline, gabazine, and picrotoxin, and the selective GABAB antagonists, 2-OH-saclofen and CGP-55845A, on the spontaneous activity of electrophysiologically identified substantia nigra dopaminergic neurons were recorded in vivo in urethane anesthetized rats. Blockade of GABAA inputs by bicuculline powerfully and reversibly induced burst Firing in dopaminergic neurons along with a modest (25%) increase in Firing rate, but the increase in burst Firing was not correlated with the increase in Firing rate. Picrotoxin and gabazine also produced an increase in burst Firing without an increase in Firing rate. In contrast, local application of GABAB antagonists did not produce bursting but rather caused a modest shift to a more regular Firing Pattern in 50% of the cases. These data demonstrate that dopaminergic neurons in vivo are under tonic GABAergic inhibition mediated by GABAA receptors and suggest that GABAergic afferents to substantia nigra comprise a major pathway by which the Firing Pattern of dopaminergic neurons is controlled in vivo. Synapse 32:165-177, 1999. r 1999 Wiley-Liss, Inc.
P Mazzone - One of the best experts on this subject based on the ideXlab platform.
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spontaneous sleep modulates the Firing Pattern of parkinsonian subthalamic nucleus
Experimental Brain Research, 2006Co-Authors: Alessandro Stefani, Salvatore Galati, Antonella Peppe, Andrea Bassi, Mariangela Pierantozzi, Atticus H Hainsworth, Giorgio Bernardi, Antonio Orlacchio, Paolo Stanzione, P MazzoneAbstract:In Parkinson's disease, the subthalamic nucleus (STN) is a common target for functional neurosurgery. Recent investigations have suggested that physiological non-motor stimuli may dramatically alter STN Firing properties. By maintaining long-lasting micro-recordings of STN single units in Parkinson's disease (PD) patients, here we show that the neurons that are responsive to passive movements are also strongly modulated by altered vigilance state (awake vs. sleep). In addition, sleep was characterized by a distinctive irregular train-like Firing Pattern. These findings suggest that the reduction of the somato-sensory input modifies rigidity and, hence, STN discharge mode. Further, it is suggested that specific STN electrophysiological features are potential targets for future therapeutic interventions.
Elisabeth Lambert - One of the best experts on this subject based on the ideXlab platform.
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change in sympathetic nerve Firing Pattern associated with dietary weight loss in the metabolic syndrome
Frontiers in Physiology, 2011Co-Authors: Elisabeth Lambert, Nora E Straznicky, Tye Dawood, Carolina Ikasari, Mariee T Grima, Murray D Esler, Markus P Schlaich, Gavin W LambertAbstract:Sympathetic activation in subjects with the metabolic syndrome (MS) plays a role in the pathogenesis of cardiovascular disease development. Diet-induced weight loss decreases sympathetic outflow. However the mechanisms that account for sympathetic inhibition are not known. We sought to provide a detailed description of the sympathetic response to diet by analyzing the Firing behavior of single-unit sympathetic nerve fibres. Fourteen subjects (57±2 years, 9 men, 5 females) fulfilling ATP III criteria for the MS underwent a 3-month low calorie diet. Metabolic profile, hemodynamic parameters and multi-unit and single unit muscle sympathetic nerve activity (MSNA, microneurography) were assessed prior to and at the end of the diet. Patients’ weight dropped from 96±4 to 88±3 kg (P<0.001). This was associated with a decrease in systolic and diastolic blood pressure (-12 ±3 and -5±2 mmHg, P<0.05), and in heart rate (-7±2 bpm, P<0.01) and an improvement in all metabolic parameters (fasting glucose: -0.302.1±0.118 mmol/l, total cholesterol: -0.564±0.164 mmol/l, triglycerides: -0.414±0.137 mmol/l, P<0.05). Multi-unit MSNA decreased from 68±4 to 59±5 bursts per 100 heartbeats (P<0.05). Single-unit MSNA indicated that the Firing rate of individual vasoconstrictor fibres decreased from 59±10 to 32±4 spikes per 100 heart beats (P<0.05). The probability of Firing decreased from 34±5 to 23±3 % of heartbeats (P<0.05), and the incidence of multiple Firing decreased from 14±4 to 6±1 % of heartbeats (P<0.05). Cardiac and sympathetic baroreflex function were significantly improved (cardiac slope: 6.57±0.69 to 9.57±1.20 msec.mmHg-1; sympathetic slope: -3.86±0.34 to -5.05±0.47 bursts per 100 heartbeats.mmHg-1 P<0.05 for both). Hypocaloric diet decreased sympathetic activity and improved hemodynamic and metabolic parameters. The sympathoinhibition associated with weight loss involves marked changes, not only in the rate but also in the Firing Pattern of active vasoconstrictive fibres.
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single unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover
The Journal of Physiology, 2011Co-Authors: Elisabeth Lambert, Tye Dawood, Markus P Schlaich, Carolina I Sari, Reena Chopra, David Barton, David M Kaye, Mikael Elam, Murray D EslerAbstract:Non-technical summary Recent work has demonstrated differences in the Firing Pattern of sympathetic nerves in a variety of patient groups. The significance or consequences of this Firing Pattern remain unknown. We examined whether the nerve Firing Pattern was associated with increased noradrenaline release from the heart. The activity and Pattern of the nerve Firing was recorded in the peroneal nerve and subjects were divided into two groups according to the Firing Pattern as ‘low Firing rate’ or ‘high Firing rate’. In those with a high Firing rate, the noradrenaline released by the heart was two times higher than that of subjects with a low Firing rate. This study indicates that the nerve Firing Pattern may dictate the amount of noradrenaline released by the heart. Abstract Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the Firing Pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve Firing Pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit Firing Patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n= 6), depression (n= 7) and panic disorder (n= 9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve Firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the Firing Pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher Firing rates (P < 0.0001) and increased probability of Firing (P < 0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve Firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min−1, P < 0.05). This study indicates that multiple within-burst Firing and increased single-unit Firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover.
Carlos A. Paladini - One of the best experts on this subject based on the ideXlab platform.
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dopamine controls the Firing Pattern of dopamine neurons via a network feedback mechanism
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Carlos A. Paladini, Siobhan Robinson, Hitoshi Morikawa, John T Williams, Richard D PalmiterAbstract:Changes in the Firing Pattern of midbrain dopamine neurons are thought to encode information for certain types of reward-related learning. In particular, the burst Pattern of Firing is predicted to result in more efficient dopamine release at target loci, which could underlie changes in synaptic plasticity. In this study, the effects of dopamine on the Firing Patterns of dopaminergic neurons in vivo and their electrophysiological characteristics in vitro were examined by using a genetic dopamine-deficient (DD) mouse model. Extracellular recordings in vivo showed that, although the Firing Pattern of dopamine neurons in normal mice included bursting activity, DD mice recordings showed only a single-spike Pattern of activity with no bursts. Bursting was restored in DD mice after systemic administration of the dopamine precursor, l-3,4-dihydroxyphenylalanine (l-dopa). Whole-cell recordings in vitro demonstrated that the basic electrophysiology and pharmacology of dopamine neurons were identical between DD and control mice, except that amphetamine did not elicit a hyperpolarizing current in slices from DD mice. These data suggest that endogenously released dopamine plays a critical role in the afferent control of dopamine neuron bursting activity and that this control is exerted via a network feedback mechanism.
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GABAA and GABAB antagonists differentially affect the Firing Pattern of substantia nigra dopaminergic neurons in vivo
Synapse (New York N.Y.), 1999Co-Authors: Carlos A. Paladini, James M. TepperAbstract:The effects of local pressure application of the selective GABAA antago- nists, bicuculline, gabazine, and picrotoxin, and the selective GABAB antagonists, 2-OH-saclofen and CGP-55845A, on the spontaneous activity of electrophysiologically identified substantia nigra dopaminergic neurons were recorded in vivo in urethane anesthetized rats. Blockade of GABAA inputs by bicuculline powerfully and reversibly induced burst Firing in dopaminergic neurons along with a modest (25%) increase in Firing rate, but the increase in burst Firing was not correlated with the increase in Firing rate. Picrotoxin and gabazine also produced an increase in burst Firing without an increase in Firing rate. In contrast, local application of GABAB antagonists did not produce bursting but rather caused a modest shift to a more regular Firing Pattern in 50% of the cases. These data demonstrate that dopaminergic neurons in vivo are under tonic GABAergic inhibition mediated by GABAA receptors and suggest that GABAergic afferents to substantia nigra comprise a major pathway by which the Firing Pattern of dopaminergic neurons is controlled in vivo. Synapse 32:165-177, 1999. r 1999 Wiley-Liss, Inc.