References of "Seutin, Vincent"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailSubsaturation of the NMDAR glycine site allows the regulation of bursting activity in juvenile rat nigral dopamine neurons
Destreel, Geoffrey ULiege; Seutin, Vincent ULiege; Engel, Dominique ULiege

in European Journal of Neuroscience (2019)

The activation of N-methyl-D-aspartate receptors (NMDARs) in substantia nigra pars compacta (SNc) dopamine (DA) cells is central to generate the bursting activity, a phasic signal linked to DA related ... [more ▼]

The activation of N-methyl-D-aspartate receptors (NMDARs) in substantia nigra pars compacta (SNc) dopamine (DA) cells is central to generate the bursting activity, a phasic signal linked to DA related behaviors via the change in postsynaptic DA release. NMDARs are recruited during excitatory synaptic transmission by glutamate release but the glycine site level of occupancy of these receptors during basal action potential-dependent activity is not known for SNc DA neurons. We explored NMDARdependent signals during exogenous applications of co-agonists in midbrain slices from juvenile rats. We found that both glycine and D-serine strengthened the NMDAR-dependent component of excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner. EPSCs were also increased by endogenous glycine via the blockade of the glycine transport. The glycine site of NMDARs contributing to synaptic transmission is therefore subsaturated. The behaviorally relevant burst firing was more sensitive to exogenous D-serine and endogenous glycine than to exogenous glycine. The mechanisms regulating the availability of the co-agonists exert consequently a critical influence on the excitability of DA neurons via NMDARs. The modulation of the phasic firing in DA neurons by ambient NMDAR co-agonists may be important for nigral information processing and downstream motor-related behavior. [less ▲]

Detailed reference viewed: 22 (2 ULiège)
Full Text
See detailEffect of Amphetamine on Ventral Tegmental Area Neurons in awake Rats
Delairesse, Charlotte ULiege; Koulchitsky, Stanislav ULiege; Seutin, Vincent ULiege

Poster (2018, December 18)

Amphetamine (AMPH) is an addictive psychostimulant targeting the dopamine system. But its effect on the neurons of this system is still unclear. Here, we studied the effects of amphetamine on the firing ... [more ▼]

Amphetamine (AMPH) is an addictive psychostimulant targeting the dopamine system. But its effect on the neurons of this system is still unclear. Here, we studied the effects of amphetamine on the firing rate of dopamine (DA) and non-dopamine neurons of the ventral tegmental area, a key structure in the reward circuit, of awake rats. Using wireless neural probes to investigate the electrical activity of the neurons in freely moving rats, we observed that acute injection of AMPH is followed by a decrease of firing rate of most of registered DA units. The remaining population of DA units either increased or did not significantly change their activity. At the same time, AMPH stimulated the locomotor activity and induced a stereotypic behavior. (FR) L'amphétamine (AMPH) est un psychostimulant addictif visant le système dopaminergique. Cependant, ses effets sur les neurones de ce système sont nébuleux. Nous étudions les effets de l'AMPH sur la fréquence de décharge des neurones dopaminergiques et non dopaminergique de l'aire tegmentale ventrale, une structure clef du circuit de la récompense, de rats éveillés. En utilisant un système d'électrodes sans fil pour étudier l'activité électrique des neurones de rats libres de leurs mouvements, nous avons observer que l'injection aiguë d'AMPH est suivie d'une diminution de la fréquence de décharge de la majorité des neurones dopaminergiques enregistrés. Le reste des neurones dopaminergique présentaient une activité augmentée ou qui ne subissait pas de changement significatif. En même temps, l'AMPh stimule l'activité locomotrice et induit un comportement stéréotypé. [less ▲]

Detailed reference viewed: 18 (1 ULiège)
Full Text
See detailExpérimentation animale: la recette d'une polémique scientifique
Muraille, Eric; de kerchove, Alban; Muylkens, Benoit et al

Article for general public (2018)

La majorité du grand public accepte l’expérimentation animale à condition que celle-ci contribue à l’amélioration de la santé humaine et qu’aucune autre alternative n’existe. En face, les opposants ... [more ▼]

La majorité du grand public accepte l’expérimentation animale à condition que celle-ci contribue à l’amélioration de la santé humaine et qu’aucune autre alternative n’existe. En face, les opposants décrédibilisent la recherche et stigmatise une profession à des fins idéologiques. Relevé de leurs arguments. [less ▲]

Detailed reference viewed: 63 (5 ULiège)
Full Text
See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

Detailed reference viewed: 226 (60 ULiège)
Full Text
See detailL'expérimentation animale ne se fait pas en dehors de tout contrôle (OPINION)
Muraille, Eric; de Kerchove d'Exaerde, Alban; Blanpain, Cedric et al

Article for general public (2018)

Proposer de réduire l'expérimentation animale pour raisons morales est louable. Mais ce choix de société ne doit pas être vendu au citoyen en lui laissant croire que la recherche conserverait la même ... [more ▼]

Proposer de réduire l'expérimentation animale pour raisons morales est louable. Mais ce choix de société ne doit pas être vendu au citoyen en lui laissant croire que la recherche conserverait la même qualité ou en serait améliorée. [less ▲]

Detailed reference viewed: 62 (11 ULiège)
Full Text
See detailAnalyse détaillée de la seconde version de l’avant-projet de Code du bien-être animal wallon. Lecture commentée au 21/03/2018 du Chapitre 8 (Expérimentation animale)
Drion, Pierre ULiege; Corhay, Albert ULiege; Haubruge, Eric ULiege et al

Report (2018)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984 et ses modifications, aujourd’hui, le projet de code pour la Région wallonne). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la Directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

Detailed reference viewed: 93 (11 ULiège)
Full Text
See detailL’expérimentation animale reste indispensable (OPINION)
Amorim, Christiani; Andris, Fabienne; Arckens, Lut et al

Article for general public (2017)

Trop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle.

Detailed reference viewed: 106 (28 ULiège)
Full Text
See detailModulation of NMDA receptor mediated excitatory synaptic currents in dopamine neurons of the substantia nigra.
Destreel, Geoffrey ULiege; Seutin, Vincent ULiege; Engel, Dominique ULiege

Poster (2017, November 08)

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in ... [more ▼]

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in target areas depends on the presynaptic AP firing pattern and is essential to modulate several aspects of behavior such as the control of movement. Bursting activity is mediated by excitatory afferents and specifically by the activation of NMDA receptors (NMDARs). However, the level of activation of NMDARs at these synapses during spontaneous synaptic activity is unknown. We assessed the occupancy of the glycine binding sites of the NMDAR by testing the effects of coagonists and by blocking the uptake of glycine on spontaneous excitatory postsynaptic currents (sEPSCs) in DA neurons of the SNc. [less ▲]

Detailed reference viewed: 39 (11 ULiège)
Full Text
See detailAvant-projet de décret relatif au Code wallon du Bien-être des animaux Lecture commentée au 04 juillet 2017 des chap. 4, 8, 11
Drion, Pierre ULiege; Seutin, Vincent ULiege; Balthazart, Jacques ULiege et al

Report (2017)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984, aujourd’hui, le projet de code). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

Detailed reference viewed: 46 (4 ULiège)
Full Text
See detailModulation of NMDA receptor mediated excitatory synaptic currents in dopamine neurons of the substantia nigra
Destreel, Geoffrey ULiege; Seutin, Vincent ULiege; Engel, Dominique ULiege

Poster (2017, May 17)

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in ... [more ▼]

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in target areas depends on the presynaptic AP firing pattern and is essential to modulate several aspects of behavior such as the control of movement. Bursting activity is mediated by excitatory afferents and specifically by the activation of NMDA receptors (NMDARs). However, the level of activation of NMDARs at these synapses during spontaneous synaptic activity is unknown. We assessed the occupancy of the glycine binding sites of the NMDAR by testing the effects of coagonists and by blocking the uptake of glycine on spontaneous excitatory postsynaptic currents (sEPSCs) in DA neurons of the SNc. Parasagittal midbrain slices (300 – 350 µm thickness) were cut from the brains 16- to 26- days old Wistar rats using a vibratome. Whole-cell recordings were made using warm (~35C°) standard artificial cerebrospinal fluid. sEPSCs were pharmacologically isolated and recorded at +40 and -70 mV. A large NMDAR-sEPSC component was present at +40 mV as revealed by the application of 50 µM D-AP5 (n=8, P < 0.001). At -70 mV, D-AP5 had no effect on the EPSC, as expected (n=7, P = 0.52). The mean amplitude of the average NMDAR sEPSC measured at +40 mV increased significantly from 8.6 ± 0.8 pA in control conditions to 10.9 ± 1.0 pA during bath application of 300 μM glycine (n=10, P < 0.001). We also investigated the effect of D-serine, the other coagonist at the NMDAR glycine site. The mean NMDAR EPSC amplitude measured at +40 mV showed a tendency toward larger values, from 6.8 ± 0.8 pA in control conditions to 8.8 ± 1.1 pA in the presence of 100 µM D-serine (n=4). Blockade of the glycine transporter-1 (GlyT1) significantly increased the mean amplitude of NMDAR sEPSCs measured at +40 mV from 7.1 ± 0.5 pA in control conditions to 10.5 ± 0.8 pA in the presence of 5 μM NFPS (n=8, P < 0.001). At -70 mV, NFPS had no effect on the AMPAR-sEPSC component, as expected (n=8, P = 0.23). In conclusion, our results indicate that the NMDAR glycine sites are not saturated by glycine and D-serine during sEPSCs in control conditions. [less ▲]

Detailed reference viewed: 52 (25 ULiège)
See detailModulation of NMDA receptor mediated excitatory synaptic currents in dopamine neurons of the substantia nigra.
Destreel, Geoffrey ULiege; Seutin, Vincent ULiege; Engel, Dominique ULiege

Poster (2017, March 17)

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in ... [more ▼]

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in target areas depends on the presynaptic AP firing pattern and is essential to modulate several aspects of behavior such as the control of movement. Bursting activity is mediated by excitatory afferents and specifically by the activation of NMDA receptors (NMDARs). However, the level of activation of NMDARs at these synapses during spontaneous synaptic activity is unknown. We assessed the occupancy of the glycine binding sites of the NMDAR by testing the effects of coagonists and by blocking the uptake of glycine on spontaneous excitatory postsynaptic currents (sEPSCs) in DA neurons of the SNc. Parasagittal midbrain slices (300 – 350 µm thickness) were cut from the brains 16- to 26- days old Wistar rats using a vibratome. Whole-cell recordings were made using warm (~35C°) standard artificial cerebrospinal fluid. sEPSCs were pharmacologically isolated and recorded at +40 and -70 mV. A large NMDAR-sEPSC component was present at +40 mV as revealed by the application of 50 µM D-AP5 (n=8, P < 0.001). At -70 mV, D-AP5 had no effect on the EPSC, as expected (n=7, P = 0.52). The mean amplitude of the average NMDAR sEPSC measured at +40 mV increased significantly from 8.6 ± 0.8 pA in control conditions to 10.9 ± 1.0 pA during bath application of 300 μM glycine (n=10, P < 0.001). We also investigated the effect of D-serine, the other coagonist at the NMDAR glycine site. The mean NMDAR EPSC amplitude measured at +40 mV showed a tendency toward larger values, from 6.8 ± 0.8 pA in control conditions to 8.8 ± 1.1 pA in the presence of 100 µM D-serine (n=4). Blockade of the glycine transporter-1 (GlyT1) significantly increased the mean amplitude of NMDAR sEPSCs measured at +40 mV from 7.1 ± 0.5 pA in control conditions to 10.5 ± 0.8 pA in the presence of 5 μM NFPS (n=8, P < 0.001). At -70 mV, NFPS had no effect on the AMPAR-sEPSC component, as expected (n=8, P = 0.23). In conclusion, our results indicate that the NMDAR glycine sites are not saturated by glycine and D-serine during sEPSCs in control conditions. [less ▲]

Detailed reference viewed: 67 (21 ULiège)
Full Text
See detailEffect of electrode morphology on the frquency spectrum of local field potentials in the rat ventral tegmental area
Delairesse, Charlotte ULiege; Seutin, Vincent ULiege; Koulchitsky, Stanislav ULiege

Poster (2016, November 14)

Implantable microelectrode arrays for chronic neural recordings receive an attention by a number of research groups investigating ensemble spike activity and local field potentials. Due to that interest ... [more ▼]

Implantable microelectrode arrays for chronic neural recordings receive an attention by a number of research groups investigating ensemble spike activity and local field potentials. Due to that interest, various types of arrays have been developed. In the present study we compared the LFP signals recorded from the ventral tegmental area (VTA) of freely moving male Wistar rats using the two types of arrays: microelectrode microwire arrays, and silicon-based planar probes. Our choice was based on the difference in the geometry of these two array types. The microwire electrodes have a three-dimensional recording surface around their tips. This allows them to receive the signal from the diverse brain regions. In contrast, the electrode contacts of the planar probe are patterned on one side of the silicon shaft (often named top-side, in contrast to the other, back-side). This configuration mainly allows registering the signal from the top-side of the shaft, while the signal from the back-side gets attenuated. Microwire arrays used in this study consisted of 8 sharpened platinum iridium wires, coated with parylene-C, except for the tip allowing the recording (Alpha Omega GmbH, Israel). Planar probes (ATLAS Neuroengineering, Belgium) had 16 iridium oxide electrode contacts implemented in the 4 silicon shafts, 4 electrode contacts per shaft. The recording was performed using a wireless system (W-Basic-System, Multi Channel Systems MCS GmbH, Germany). The probes were implanted in two orientations: top-side facing the midline, and top-side facing the lateral plane of the brain. For verification of the recording area the rats were anaesthetized and perfused with 4% paraformaldehyde containing 1 % of Gadovist. The brains were removed from the skull and placed in Fomblin for MRI scanning (9.4 Tesla MRI DirectDrive VNMRS, Agilent Technologies, Palo Alto, CA). Frequency spectra of LFP recorded by the microwire arrays, and by the planar probes oriented to the lateral plane of the brain contained a prominent peak in the theta range (6-8 Hz). In contrast, the signal registered using the planar probes oriented to the midline lacked such a peak and was more heterogeneous. We attribute the observed difference to the geometry of the recording platforms. [less ▲]

Detailed reference viewed: 17 (1 ULiège)
Full Text
Peer Reviewed
See detailInteractions between calcium channels and SK channels in midbrain dopamine neurons and their impact on pacemaker regularity: Contrasting roles of N- and L-type channels.
de Vrind, V.; Scuvée-Moreau, Jacqueline ULiege; Drion, Guillaume ULiege et al

in European Journal of Pharmacology (2016), 788

Although small-conductance Ca2+-activated K+ (SK) channels and various types of voltage-gated Ca2+ (Cav) channels have been described in midbrain dopaminergic neurons, the nature of their interactions is ... [more ▼]

Although small-conductance Ca2+-activated K+ (SK) channels and various types of voltage-gated Ca2+ (Cav) channels have been described in midbrain dopaminergic neurons, the nature of their interactions is unclear. More particularly, the role of various Cav channel types in either promoting irregularity of firing (by generating an inward current during SK channel blockade) or promoting regularity of firing (by providing the source of Ca2+ for the activation of SK channels) has not been systematically explored. We addressed this question using intracellular and extracellular recordings from substantia nigra, pars compacta (SNc), dopaminergic neurons in rat midbrain slices. Neurons were pharmacologically isolated from their differences. When examining the ability of various Cav channel blockers to inhibit the SK-mediated afterhyperpolarization (AHP), we found that only the N-type Cav channel blocker ω-conotoxin-GVIA was able to reduce the apamin-sensitive AHP, but only partially (~40%). Specific blockers of L, P/Q, T or R channels had no effect on this AHP. Combining ω-conotoxin-GVIA and other specific blockers did not yield greater block and even the broad Cav blocker Cd2+ induced a submaximal (~75%) effect. Extracellular recordings examining firing regularity yielded congruent results: none of the specific blockers was able to increase firing irregularity to the extent that the specific SK blocker apamin did. The irregularity of firing observed with apamin could only be reversed by blocking L-type Ca2+ channels. Thus various sources of Ca2+ appear to be required for SK channel activation in SNc neurons (some of them still unidentified), ensuring robustness of pacemaking regularity. [less ▲]

Detailed reference viewed: 57 (20 ULiège)
See detailModulation of NMDA receptor mediated excitatory synaptic currents in dopamine neurons of the substantia nigra.
Destreel, Geoffrey ULiege; Seutin, Vincent ULiege; Engel, Dominique ULiege

Poster (2016, April 22)

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in ... [more ▼]

Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) exhibit two main firing modes, spontaneous single action potential (AP) firing and bursting. The amount of DA released by these neurons in target areas depends on the presynaptic AP firing pattern and is essential to modulate several aspects of behavior such as the control of movement. Bursting activity is mediated by excitatory afferents and specifically by the activation of NMDA receptors (NMDARs). However, the level of activation of NMDARs at these synapses during spontaneous synaptic activity is unknown. We assessed the occupancy of the glycine binding sites of the NMDAR by testing the effects of coagonists and by blocking the uptake of glycine on spontaneous excitatory postsynaptic currents (sEPSCs) in DA neurons of the SNc. Parasagittal midbrain slices (300 – 350 µm thickness) were cut from the brains 16- to 26- days old Wistar rats using a vibratome. Whole-cell recordings were made using warm (~35C°) standard artificial cerebrospinal fluid. sEPSCs were pharmacologically isolated and recorded at +40 and -70 mV. A large NMDAR-sEPSC component was present at +40 mV as revealed by the application of 50 µM D-AP5 (n=8, P < 0.001). At -70 mV, D-AP5 had no effect on the EPSC, as expected (n=7, P = 0.52). The mean amplitude of the average NMDAR sEPSC measured at +40 mV increased significantly from 8.6 ± 0.8 pA in control conditions to 10.9 ± 1.0 pA during bath application of 300 μM glycine (n=10, P < 0.001). We also investigated the effect of D-serine, the other coagonist at the NMDAR glycine site. The mean NMDAR EPSC amplitude measured at +40 mV showed a tendency toward larger values, from 6.8 ± 0.8 pA in control conditions to 8.8 ± 1.1 pA in the presence of 100 µM D-serine (n=4). Blockade of the glycine transporter-1 (GlyT1) significantly increased the mean amplitude of NMDAR sEPSCs measured at +40 mV from 7.1 ± 0.5 pA in control conditions to 10.5 ± 0.8 pA in the presence of 5 μM NFPS (n=8, P < 0.001). At -70 mV, NFPS had no effect on the AMPAR-sEPSC component, as expected (n=8, P = 0.23). In conclusion, our results indicate that the NMDAR glycine sites are not saturated by glycine and D-serine during sEPSCs in control conditions. [less ▲]

Detailed reference viewed: 24 (9 ULiège)
Full Text
Peer Reviewed
See detailDifferential somatic Ca2+ channel profile in midbrain dopaminergic neurons
Philippart, Fabian ULiege; Destreel, Geoffrey ULiege; Merino-Sepulveda, Paulina et al

in Journal of Neuroscience (2016), 36(27), 7234-7245

Dopaminergic (DA) neurons located in the ventral midbrain continuously generate a slow endogenous pacemaker activity, the mechanism of which is still debated. It has been suggested that, in the substantia ... [more ▼]

Dopaminergic (DA) neurons located in the ventral midbrain continuously generate a slow endogenous pacemaker activity, the mechanism of which is still debated. It has been suggested that, in the substantia nigra pars compacta (SNc), the pacemaking relies more on Ca2+ channels and that the density of L type Ca2+ channels is higher in these DA neurons than in those located in the ventral tegmental area (VTA). This might lead to a higher Ca2+ load in SNc DA neurons, and explain their higher susceptibility to degeneration. However, direct evidence for this hypothesis is lacking. We found that the L-type current and channel density is indeed higher in the somata of rat SNc DA neurons, and that this current undergoes less inactivation in this region. Non stationary fluctuation analysis (NSFA) measurements showed a much higher number of L-type channels in the soma of SNc DA neurons, as well as a smaller single channel conductance, pointing to a possible different molecular identity of L-type channels in DA neurons from the two areas. A major consequence of this is that pacemaking and even more so bursting are associated with a larger Ca2+ entry through L-type channels in SN DA neurons than in their VTA counterparts. Our results establish a molecular and functional difference between two populations of midbrain DA neurons that may contribute to their differential sensitivity to neurodegeneration. [less ▲]

Detailed reference viewed: 58 (20 ULiège)
Full Text
Peer Reviewed
See detailDopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects.
Borgs, Laurence; Peyre, Elise ULiege; Alix, Philippe et al

in Scientific Reports (2016), 6

Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of ... [more ▼]

Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons. Here we show that NSCs bearing the mutation tend to differentiate less efficiently into dopaminergic neurons and that the latter exhibit significant branching defects as compared to their controls. [less ▲]

Detailed reference viewed: 50 (13 ULiège)
Full Text
Peer Reviewed
See detailMecanismes de l'effet diuretique de la cafeine.
Marx, Barbara; Scuvee, Eleonore; Scuvée-Moreau, Jacqueline ULiege et al

in MS. Medecine Sciences (2016), 32(5), 485-90

Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. Caffeine competitively antagonizes the adenosine receptors (AR), which are G protein ... [more ▼]

Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. Caffeine competitively antagonizes the adenosine receptors (AR), which are G protein-coupled receptors largely distributed throughout the body, including brain, heart, vessels and kidneys. Caffeine consumption has a well-known diuretic effect. The homeostasis of salt and water involves different segments of the nephron, in which adenosine plays complex roles depending on the differential expression of AR. Hence, caffeine increases glomerular filtration rate by opposing the vasoconstriction of renal afferent arteriole mediated by adenosine via type 1 AR during the tubuloglomerular feedback. Caffeine also inhibits Na(+) reabsorption at the level of renal proximal tubules. In addition, caffeine perturbs the hepatorenal reflex via sensory nerves in Mall's intrahepatic spaces. Here, we review the physiology of caffeine-induced natriuresis and diuresis, as well as the putative pathological implications. [less ▲]

Detailed reference viewed: 193 (19 ULiège)
Full Text
Peer Reviewed
See detailCorrelation between ethanol behavioral sensitization and midbrain dopamine neuron reactivity to ethanol
Didone, Vincent ULiege; Masson, Sébastien; Quoilin, Caroline et al

in Addiction Biology (2016), 21(2), 387-396

Repeated ethanol injections lead to a sensitization of its stimulant effects in mice. Some recent results argue against a role for ventral tegmental area (VTA) dopamine neurons in ethanol behavioral ... [more ▼]

Repeated ethanol injections lead to a sensitization of its stimulant effects in mice. Some recent results argue against a role for ventral tegmental area (VTA) dopamine neurons in ethanol behavioral sensitization. The aim of the present study was to test whether in vivo ethanol locomotor sensitization correlates with changes in either basal- or ethanol evoked firing rates of dopamine neurons in vitro. Female Swiss mice were daily injected with 2.5 g/kg ethanol (or saline in the control group) for 7 days and their locomotor activity was recorded. At the end of the sensitization procedure, extracellular recordings were made from dopaminergic neurons in midbrain slices from these mice. Significantly higher spontaneous basal firing rates of dopamine neurons were recorded in ethanol-sensitized mice relative to control mice, but without correlations with the behavioral effects. The superfusion of sulpiride, a dopamine D2 antagonist, induced a stronger increase of dopamine neuron firing rates in ethanol-sensitized mice. This shows that the D2 feedback in dopamine neurons is preserved after chronic ethanol administration and argues against a reduced D2 feedback as an explanation for the increased dopamine neuron basal firing rates in ethanol-sensitized mice. Finally, ethanol superfusion (10–100 mM) significantly increased the firing rates of dopamine neurons and this effect was of higher magnitude in ethanol-sensitized mice. Furthermore, there were significant correlations between such a sensitization of dopamine neuron activity and ethanol behavioral sensitization. These results support the hypothesis that changes in brain dopamine neuron activity contribute to the behavioral sensitization of the stimulant effects of ethanol. [less ▲]

Detailed reference viewed: 81 (27 ULiège)
Full Text
Peer Reviewed
See detailHigh dendritic expression of Ih in the proximity of the axon origin controls the integrative properties of nigral dopamine neurons.
Engel, Dominique ULiege; Seutin, Vincent ULiege

in Journal of Physiology (2015), 593(22), 4905-4922

Dendrites of most neurons express voltage-gated ion channels in their membrane. In combination with passive properties, active currents confer to dendrites a high computational potential. The ... [more ▼]

Dendrites of most neurons express voltage-gated ion channels in their membrane. In combination with passive properties, active currents confer to dendrites a high computational potential. The hyperpolarization-activated cation current Ih present in the dendrites of some pyramidal neurons affects their membrane and integration properties, synaptic plasticity and higher functions such as memory. A gradient of increasing h-channel density towards distal dendrites has been found to be responsible for the location independence of excitatory postsynaptic potential (EPSP) waveform and temporal summation in cortical and hippocampal pyramidal cells. However, reports on other cell types revealed that smoother gradients or even linear distributions of Ih can achieve homogeneous temporal summation. Although the existence of a robust, slowly activating Ih current has been repeatedly demonstrated in nigral dopamine neurons, its subcellular distribution and precise role in synaptic integration are unknown. Using cell-attached patch-clamp recordings, we find a higher Ih current density in the axon-bearing dendrite than in the soma or in dendrites without axon in nigral dopamine neurons. Ih is mainly concentrated in the dendritic membrane area surrounding the axon origin and decreases with increasing distances from this site. Single EPSPs and temporal summation are similarly affected by blockade of Ih in axon- and non-axon-bearing dendrites. The presence of Ih close to the axon is pivotal to control the integrative functions and the output signal of dopamine neurons and may consequently influence the downstream coding of movement. [less ▲]

Detailed reference viewed: 23 (6 ULiège)