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A Guyon

Publications and source records attributed to A Guyon.

At least 19 recordsLinked to original sources
PubMed2006

Stromal cell-derived factor-1alpha modulation of the excitability of rat substantia nigra dopaminergic neurones: presynaptic mechanisms.

In rat substantia nigra (SN), Chemokine (CXC motif) receptor 4 (CXCR4) for the chemokine stromal cell-derived factor (SDF)-1alpha is expressed on dopaminergic (DA) neurones, but also on non-DA cells, suggesting presynaptic actions. Using whole-cell patch-clamp recordings in DA neurones of rat SN slices at a holding potential of -60 mV, we showed here that SDF-1alpha exerts multiple presynaptic effects. First, SDF-1alpha (10 nm) induced an increase in the frequency of spontaneous and miniature GABA(A) postsynaptic currents by presynaptic mechanisms, consistent with the presence of CXCR4 on GABAergic neurones of the SN, as revealed by immunocytochemistry. Second, SDF-1alpha (0.1-1 nm) induced a glutamatergic inward current resistant to tetrodotoxin (TTX), most probably the result of glutamate release from non-neuronal cells. This inward current was not blocked by the CXCR4 antagonist AMD 3100 (1 microm), consistent with the lack of CXCR4 on astrocytes as shown by immunocytochemistry under basal conditions. Finally, SDF-1alpha (10 nm) induced, via CXCR4, an outward G protein-activated inward rectifier (GIRK) current, which was TTX sensitive and prevented by application of the GABA(B) antagonist CGP55845A, suggesting GABA spillover on to GABA(B) receptors. Our results show that SDF-1alpha induces, via presynaptic mechanisms, alterations in the excitability of DA neurones as confirmed by current-clamp experiments.

Animals↗
PubMed2005

Complex effects of stromal cell-derived factor-1 alpha on melanin-concentrating hormone neuron excitability.

Stromal cell-derived factor 1alpha (SDF-1alpha), a chemoattractant for leucocytes and neurons, and its receptor, CXCR4 are expressed in subsets of neurons of specific brain areas. In rat lateral hypothalamic area (LHA) we show, using immunocytochemistry, that CXCR4 is localized within melanin-concentrating hormone (MCH)-expressing neurons, mainly involved in feeding behaviour regulation. We investigated whether SDF-1alpha may control MCH neuronal activity. Patch-clamp recordings in rat LHA slices revealed multiple effects of SDF-1alpha on the membrane potential of MCH neurons, indirect through glutamate/GABA release and direct through GIRK current activation. Moreover, SDF-1alpha at 0.1-1 nM decreased peak and discharge frequency of action potential evoked by current pulses. These effects were further confirmed in voltage-clamp experiments, SDF-1alpha depressing both potassium and sodium currents. At 10 nM, however, SDF-1alpha increased peak and discharge frequency of action potential evoked by current pulses. Using a specific CXCR4 antagonist, we demonstrated that only the depressing effect on AP discharge was mediated through CXCR4 while the opposite effect was indirect. Together, our studies reveal for the first time a direct effect of SDF-1alpha on voltage-dependent membrane currents of neurons in brain slices and suggest that this chemokine may regulate MCH neuron activity.

Animals↗
PubMed2005

Stromal cell-derived factor-1alpha directly modulates voltage-dependent currents of the action potential in mammalian neuronal cells.

Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemokine whose receptor, CXCR4, is distributed in specific brain areas including hypothalamus. SDF-1alpha has recently been found to play important roles in neurons, although direct modulation of voltage-gated ionic channels has never been shown. In order to clarify this issue, we performed patch-clamp experiments in fetal mouse hypothalamic neurons in culture. SDF-1alpha (10 nm) decreased the peak and rising slope of the action potentials and spike discharge frequency in 22% of hypothalamic neurons tested. This effect was blocked by the CXCR4 antagonist AMD 3100 (1 microm) but not by the metabotropic glutamate receptor antagonist MCPG (500 microm), indicating a direct action of SDF-1alpha on its cognate receptor. This effect involved a depression of both inward and outward voltage-dependent currents of the action potential. We confirmed these effects in the human neuroblastoma cell line SH-SY5Y, which endogenously expresses CXCR4. Voltage-clamp experiments revealed that SDF-1alpha induced a 20% decrease in the peak of the tetrodotoxin-sensitive sodium current and tetraethylammonium-sensitive delayed rectifier potassium current, respectively. Both effects were concentration dependent, and blocked by AMD 3100 (200 nm). This dual effect was reduced or blocked by 0.4 mm GTPgammaS G-protein pre-activation or by pre-treatment with the G-protein inhibitor pertussis toxin (200 ng/mL), suggesting that it is mediated via activation of a G(i/o) protein. This study extends the functions of SDF-1alpha to a direct modulation of voltage-dependent membrane currents of neuronal cells.

Action Potentials↗
PubMed2003

KINKY POLLEN encodes a SABRE-like protein required for tip growth in Arabidopsis and conserved among eukaryotes.

In higher plants, pollen tubes and root hairs share an ancient growth process named tip growth. We have isolated three allelic Arabidopsis mutant lines showing kinky-shaped pollen tubes and, when homozygous, showing shorter and thicker root hairs. The ultrastructure of pollen tubes in these kinky pollen (kip) mutants is similar to that of the wild type; however, time-lapse studies suggest that aberrant pollen tube shape is caused by periodic growth arrests alternated with phases of tube axis reorientation. The KIP gene encodes a protein of 2587 amino acids that is predicted to be targeted to the secretory pathway. KIP mRNA was detected in all organs investigated but was most abundant in pollen and roots. KIP has putative homologues in many eukaryotes, including mammals and yeast, and is similar to the Arabidopsis SABRE gene, whose mutation causes a dwarf phenotype. The phenotype of the kip/sab double mutant suggests related functions for both genes, however, the KIP protein is mostly required for tip-growth.

Arabidopsis↗
PubMed2002

Functional glycine receptor maturation in the absence of glycinergic input in dopaminergic neurones of the rat substantia nigra.

The postnatal maturation pattern of glycine receptor channels (GlyRs) expressed by dopaminergic (DA) neurones of the rat substantia nigra pars compacta (SNc) was investigated using single-channel and whole-cell patch-clamp recordings in brain slices from rats aged 7-21 postnatal days (P). In neonatal rats (P7-P10), GlyRs exhibited a main conductance state of 100-110 pS with a mean open time of 16 ms. In juvenile rats (P19-P22), both the GlyR main conductance state (46-55 pS) and the mean open time (6.8 ms) were decreased. In neonatal rats, application of 30 microM picrotoxin, which is known to block homomeric GlyRs, strongly reduced glycine-evoked responses, while it was much less effective in juvenile rats. These results suggest that these GlyRs correspond functionally to alpha(2) homomeric GlyRs in neonatal rats and alpha(1)/beta heteromeric GlyRs in juvenile rats. A drastic but transient decrease in the glycine responsiveness of DA neurones occurred around P17 concomitant to the functional switch from the homomeric state to the heteromeric state. This age corresponds to a maturation phase for DA neurones. The application of 1 microM gabazine blocked spontaneous or evoked inhibitory synaptic current, while the addition of 1 microM strychnine had no effect, suggesting a lack of functional glycinergic synapses on DA neurones. Although it has been proposed that taurine is co-released with GABA at GABAergic synapses on DA neurones, in the present study the stimulation of GABAergic fibres failed to activate GlyRs. Blockade of taurine transporters and applications of high K(+) and hyposmotic solutions were also unable to induce any strychnine-sensitive current. We conclude that functional maturation of GlyRs can occur in the absence of any detectable GlyR activation in DA neurones of the SNc.

Animals↗
PubMed2002

Alpha2-adrenoceptor activation increases a cationic conductance and spontaneous GABAergic synaptic activity in dopaminergic neurones of the rat substantia nigra.

Noradrenaline (NA) plays an important role in compensating for the loss in dopaminergic (DA) function following lesions of the DA neurones of the substantia nigra (SN). Alpha2-adrenoceptors are largely expressed in these neurones, but the cellular response to their activation is unknown. Whole-cell patch-clamp recordings were made from DA neurones of rat SN. At a holding potential of -60 mV, bath application of NA (50 microM) induced an inward current (-20.3+/-10.0 pA) in 50% of the recorded neurones. This effect was mimicked by UK-14304 (50 microM), a specific alpha2-adrenoceptor agonist, whereas alpha1-adrenoceptor and beta-adrenoceptor agonists failed to induce a response. Surprisingly, alpha2-adrenoceptor antagonists (idazoxan, RX-811059, SKF-86466 and yohimbine) also induced an inward current that could occlude the one induced by UK-14304, suggesting that they may act as alpha2-adrenoceptor agonists. The inward current results from an increase in cationic conductance identical to the one previously described in these neurones, as neurotensin (1 microM), known to activate it, occluded the inward current induced by UK-14304. In addition, GABAergic miniature inhibitory postsynaptic current frequency was increased by activation of presynaptic alpha2-adrenoceptors. We conclude that the effects of NA on alpha2-adrenoceptors can contribute to the previously described composite action of NA on DA neurone firing and can be pharmacologically differentiated from the effect of NA on DA and neighbouring neurones known to be mediated through alpha1-adrenoceptors.

Action Potentials↗
PubMed1999

Incremental conductance levels of GABAA receptors in dopaminergic neurones of the rat substantia nigra pars compacta.

1. Molecular and biophysical properties of GABAA receptors of dopaminergic (DA) neurones of the pars compacta of the rat substantia nigra were studied in slices and after acute dissociation. 2. Single-cell reverse transcriptase-multiplex polymerase chain reaction confirmed that DA neurones contained mRNAs encoding for the alpha3 subunit of the GABAA receptor, but further showed the presence of alpha4 subunit mRNAs. alpha2, beta1 and gamma1 subunit mRNAs were never detected. Overall, DA neurones present a pattern of expression of GABAA receptor subunit mRNAs containing mainly alpha3/4beta2/3gamma3. 3. Outside-out patches were excised from DA neurones and GABAA single-channel patch-clamp currents were recorded under low doses (1-5 microM) of GABA or isoguvacine, a selective GABAA agonist. Recordings presented several conductance levels which appeared to be integer multiples of an elementary conductance of 4-5 pS. This property was shared by GABAA receptors of cerebellar Purkinje neurones recorded in slices (however, with an elementary conductance of 3 pS). Only the 5-6 lowest levels were analysed. 4. A progressive change in the distribution of occupancy of these levels was observed when increasing the isoguvacine concentration (up to 10 microM) as well as when adding zolpidem (20-200 nM), a drug acting at the benzodiazepine binding site: both treatments enlarged the occupancy of the highest conductance levels, while decreasing that of the smallest ones. Conversely, Zn2+ (10 microM), a negative allosteric modulator of GABAA receptor channels, decreased the occupancy of the highest levels in favour of the lowest ones. 5. These properties of alpha3/4beta2/3gamma3-containing GABAA receptors would support the hypothesis of either single GABAA receptor channels with multiple open states or that of a synchronous recruitment of GABAA receptor channels that could involve their clustering in the membranes of DA neurones.

Animals↗
PubMed1998

On the action of the anti-absence drug ethosuximide in the rat and cat thalamus.

The action of ethosuximide (ETX) on Na+, K+, and Ca2+ currents and on tonic and burst-firing patterns was investigated in rat and cat thalamic neurons in vitro by using patch and sharp microelectrode recordings. In thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75-1 mM) decreased the noninactivating Na+ current, INaP, by 60% but had no effect on the transient Na+ current. In TC neurons of the rat and cat LGN, the whole-cell transient outward current was not affected by ETX (up to 1 mM), but the sustained outward current was decreased by 39% at 20 mV in the presence of ETX (0.25-0.5 mM): this reduction was not observed in a low Ca2+ (0.5 mM) and high Mg2+ (8 mM) medium or in the presence of Ni2+ (1 mM) and Cd2+ (100 microM). In addition, ETX (up to 1 mM) had no effect on the low-threshold Ca2+ current, IT, of TC neurons of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus reticularis thalami nor on the high-threshold Ca2+ current in TC neurons of the rat LGN. Sharp microelectrode recordings in TC neurons of the rat and cat LGN and VB showed that ETX did not change the resting membrane potential but increased the apparent input resistance at potentials greater than -60 mV, resulting in an increase in tonic firing. In contrast, ETX decreased the number of action potentials in the burst evoked by a low-threshold Ca2+ potential. The frequency of the remaining action potentials in a burst also was decreased, whereas the latency of the first action potential was increased. Similar effects were observed on the burst firing evoked during intrinsic delta oscillations. These results indicate an action of ETX on INaP and on the Ca2+-activated K+ current, which explains the decrease in burst firing and the increase in tonic firing, and, together with the lack of action on low- and high-threshold Ca2+ currents, the results cast doubts on the hypothesis that a reduction of IT in thalamic neurons underlies the therapeutic action of this anti-absence medicine.

Action Potentials↗
PubMed1998

T-DNA mediated disruption of essential gametophytic genes in Arabidopsis is unexpectedly rare and cannot be inferred from segregation distortion alone.

Many genes are thought to be expressed during the haploid phase in plants, however, very few haploid-specific genes have been isolated so far. T-DNA insertion mutagenesis is a powerful tool for generating mutations that affect gametophyte viability and function, as disruption of a gene essential for these processes should lead to a defect in the transmission of the gametes. Mutants can therefore be screened on the basis of segregation distortion for a reporter resistance gene contained in the T-DNA. We have screened the Versailles collection of Arabidopsis transformants for 1:1 KanR:KanS segregation after selfing, focussing on gametophyte mutations which show normal transmission through one gametophyte and cause lethality or dysfunction of the other. Only 1.3% (207) of the 16,000 lines screened were scored as good candidates. Thorough genetic analysis of 38 putative T-DNA transmission defect lines (Ttd) identified 8 defective gametophyte mutants, which all showed 0 to 1% T-DNA transmission through the pollen. During the screen, we observed a high background of low-penetrance mutations, often affecting the function of both gametophytes, and many lines which were likely to carry chromosomal rearrangements. The reasons for the small number of retained lines (all male gametophytic) are discussed, as well as the finding that, for most of them, residual T-DNA transmission is obtained through the affected gametophyte.

Arabidopsis↗
PubMed1995

Modulation by different GABAB receptor types of voltage-activated calcium currents in rat thalamocortical neurones.

1. The effects of the GABAB receptor agonist baclofen on the voltage-dependent Ca2+ currents were studied in rat thalamocortical neurones with the use of whole cell voltage-clamp recordings in brain slices. 2. The contribution of N-, L- and P-types of Ca2+ channels to the total high voltage-activated Ca2+ (HVA Ca2+) current was assessed by the use of omega-conotoxin, nifedipine and omega-agatoxin IVA, respectively. No P-type current could be detected. Thus, the HVA Ca2+ current contained an N- and an L-type current (23 and 15% of the total current, respectively) and a residual current, which will be referred to as the 'R' component. 3. Baclofen (1-50 microM) had no effect on the low voltage-activated (LVA) Ca2+ current (IT). 4. At low concentrations (0.5-10 microM), baclofen decreased the HVA Ca2+ currents by about 10-20% without a marked modification on the kinetics, whereas 50 microM baclofen decreased the HVA Ca2+ currents by about 40% with a pronounced slowing down of the kinetics. 5. The 10-20% decrease of the total HVA Ca2+ currents produced by the low concentrations of baclofen occurred as the result of a 30% block of the 'R' component. The additional decrease observed with the dose of 50 microM was due to a full block of the N-type current. The L-type was unaffected by baclofen. 6. The effect of baclofen on the total HVA Ca2+ current was partially blocked by GABAB receptor antagonists indicating that it occurred through stimulation of GABAB receptors. 7. The effect of baclofen on the N-type current was abolished by CGP 35348 (100 microM) and CGP 55845A (100 nM). The effect on the 'R' component was also antagonized by CGP 55845A (100 nM) although with a lower potency, but was not blocked by CGP 35348 (100 microM). 8. We conclude that the effects of baclofen on the various components of the HVA Ca2+ currents occur through different types of GABAB receptors. One receptor has a high affinity for baclofen (i.e. saturated by concentrations as low as 0.5 microM), is insensitive to CGP 35348, is coupled to the 'R' component and is responsible for a maximum 20% decrease in the total HVA Ca2+ current. The other receptor has a lower affinity for baclofen (i.e. affected by a concentration of 50 microM), is sensitive to CGP 35348, is coupled to the N-type Ca2+ current and is responsible for the additional 20-30% decrease in the HVA Ca2+ current observed with 50 microM baclofen.

Animals↗
PubMed1994

Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non-NMDA receptors.

1. Intracellular and patch-clamp recordings were obtained from thalamocortical (TC) cells in the rat and cat dorsal lateral geniculate nucleus (dLGN) in vitro to study the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the synaptic potential and burst firing evoked by electrical stimulation of the optic tract. 2. At membrane potentials more positive than -65 mV, the sensory synaptic potential consisted of a fast EPSP that was followed by a smaller, slower component. At membrane potentials more negative than -65 mV, this slower component became more prominent owing to the presence of a low-threshold (LT) Ca2+ potential, which in turn evoked a high-frequency (> 150 Hz) burst of action potentials. The lower, but not the upper limit of the range of membrane potential over which burst firing occurred was dependent on the amplitude of the fast EPSP. 3. The non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) and 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3- benzodiazepine (GYKI 52466, 100 microM) greatly depressed the fast EPSP, abolished the burst firing generated by the LT Ca2+ potential, and left a relatively small, slow EPSP, which was sensitive to the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (DL-AP5, 50-100 microM). 4. In the absence of CNQX or GYKI 52466, DL-AP5 depressed the slow but not the fast EPSP. DL-AP5 also increased the latency of the first action potential evoked by the LT Ca2+ potential or even abolished the LT Ca2+ potential and associated burst firing. The latter effect was only present when this type of firing occurred within a small membrane potential range. 5. DL-AP5 had no effect on the properties of the LT Ca2+ current IT, indicating that its effect on the burst firing was not mediated by a direct action on IT. 6. The response of TC cells to high-frequency (100 Hz) stimulation consisted of an initial burst firing response, followed by a sustained depolarization that could reach firing threshold. This sustained depolarization was markedly depressed by DL-AP5 but not by CNQX. 7. These results demonstrate that with low-frequency stimulation of the sensory afferents, the generation of TC cell output in the rat and cat dLGN is mainly controlled by non-NMDA receptors, while the contribution of NMDA receptors is limited to the burst firing generated by the LT Ca2+ potential, and depends on the membrane potential range over which this type of firing occurs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

Thalamic low threshold calcium current in a genetic model of absence epilepsy.

The low threshold calcium current (IT) in thalamo-cortical neurones contributes to the generation of spike and wave discharges (SWDs) characteristic of generalized, non-convulsive absence epilepsy. The biophysical properties of this current were analysed in dorsal lateral geniculate neurones from the Genetic Absence Epilepsy Rats from Strasbourg (GAERS+). No difference was found in the voltage dependence and kinetics of IT between GAERS+ and rats of the non epileptic control strain (GAERS-). Thus, a dysfunction of IT does not appear to underlie the occurrence of SWDs in absence epilepsy.

Animals↗
PubMed1993

Potentiation by low doses of selected neuroleptics of food-induced conditioned place preference in rats.

Numerous data support the hypothesis that dopamine (DA) plays a crucial role in reward-related processes and in incentive learning in animals and man. The possibility that various neuroleptics exhibiting a high affinity for the dopaminergic D2 (and D3) receptors could reinforce DA transmission was studied using the conditioned place preference paradigm (CPP) in rats. This was done by examining the ability of these compounds to potentiate the reinforcing properties of food in hungry rats subjected to a version of the CPP paradigm which consisted of repeated pairings of food with a single environmental cue, the floor texture of an open field. During the test session when food was no longer available in the open field, the increase in the time spent by drug-free rats on the food-paired texture was assumed to indicate the perceived rewarding value of the food. This time was significantly lengthened when the specific D2 (D3)-receptor antagonists sulpiride (4 mg/kg), amisulpride (0.5, 1 mg/kg) or pimozide (0.03, 0.06 mg/kg) were administered before the food conditioning sessions. Larger doses of these compounds as well as haloperidol, metoclopramide and the non-specific D1-D2 antagonist, chlorpromazine, regardless of the doses tested, did not exhibit this effect, but rather reduced the food-induced CPP, an action usually associated with neuroleptics. The positive effects of amisulpride was reversed by a D1 receptor antagonist, SCH 23390 (0.01 mg/kg). These results suggest that, as with amphetamine (0.5 mg/kg), some D2-specific neuroleptics enhance the incentive value of food in a narrow range of low doses, an effect proposed to reflect a "prohedonic" property.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[Malignant phenylketonuria caused by biopterin synthetase deficiency. Study of neuromediator catabolites in the cerebrospinal fluid during treatment].

In a child presenting with malignant phenylketonuria due to dihydrobiopterin synthetase deficiency, the authors studied the cerebrospinal fluid (CSF) homovanillic acid and 5 hydroxyindole acetic acid levels under different circumstances: without treatment; under a treatment with tetrahydrobiopterin used alone at various doses; under a treatment associating BH4, L-dopa, 5 hydroxytryptophan and carbidopa, with increasing doses and varying administration schedules. This biological study compared with clinical evolution, shows clearly the inefficacy, regardless of the doses, of BH4 on the CSF levels of neuromediators and on the neurological status, and the excellent efficacy of neuromediator precursors provided high doses are given, divided in the nyctohemeral period.

Alcohol Oxidoreductases↗