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B Potier

Publications and source records attributed to B Potier.

At least 19 recordsLinked to original sources
PubMed2002

Decrease in calbindin content significantly alters LTP but not NMDA receptor and calcium channel properties.

The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to the synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice. We showed that long-term potentiation (LTP) induced by tetanic stimulation in CaBP-deficient mice was impaired. The fundamental biophysical properties of NMDA receptors and their number were not modified in CaBP-deficient mice. We also demonstrated that the physiological properties of calcium channels were identical between genotypes. An insufficient Ca(2+) entry through NMDA receptors or calcium channels, or a decrease in NMDA receptor density are unlikely to explain this impairment of LTP. Interestingly, we showed that the loss of LTP was not prevented by glycine but was restored in the presence of a low concentration of the NMDA receptor antagonist D-APV (5 microM) and of the calcium chelator BAPTA-AM (5 microM). Moreover, we observed a loss of LTP in the wild-type mice when the postsynaptic tetanic-induced [Ca(2+)](i) rise is excessively increased. Conversely, a weaker tetanus stimulation allowed LTP induction and maintenance in CaBP-deficient mice. These results suggest that a higher cytosol [Ca(2+)](i), due to the decrease of CaBP expression may impair LTP induction and maintenance mechanisms without affecting the mechanisms of calcium entry. Thus, CaBP plays a critical role in long term synaptic plasticity by limiting the elevation of calcium rise in the cytosol to some appropriate spatio-temporal pattern.

Animals↗
PubMed2002

Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice.

Somatostatin is implicated in a number of physiological functions in the CNS. These effects are elicited through the activation of at least five receptor subtypes. Among them, sst2 receptors appear the most widely expressed in the cortex and hippocampal region. However, the specific role of this somatostatin receptor subtype in these regions is largely undetermined. In this study, we investigated the role of the sst2 receptor in the hippocampus using mice invalidated for the sst2 gene (sst2 KO mice). Complementary experimental approaches were used. First, mice were tested in behavioral tests to explore the consequences of the gene deletion on learning and memory. Spatial discrimination learning in the radial maze was facilitated in sst2 KO mice, while operant learning of a bar-pressing task was slightly altered. Mice were then processed for electrophysiological study using the ex vivo hippocampal slice preparation. Extracellular recordings in the CA1 area showed an enhancement in glutamatergic (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the magnitude of the short-term potentiation and long-term depression. In contrast, long-term potentiation was not significantly altered. Taken together, these data demonstrate that somatostatin, acting via sst2 hippocampal receptors, may contribute to a global decrease in glutamate efficiency and consequently alter glutamate-dependent plasticity and spatial learning.

Animals↗
PubMed2001

[Programmed left ventricular stimulation in non-sustained ventricular arrhythmias].

The presence of nonsustained ventricular arrhythmia (NSVA) is an independent factor of sudden rhythmic death. The primary objective of our study was to evaluate the correlation between inducibility during programmed ventricular stimulation (PVS) and the presence of ventricular late potentials, the ejection fraction, the grade of arrhythmia, and the underlying cardiopathy. The secondary objective was to evaluate the interest of PVS in patients with NSVA. Ninety eight patients with NSVA have been tested by PVS and 14 were inducible. During the mean follow up of 24 months, 8 patients died, 3 of them suddenly. A significative statistical correlation was found between ventricular late potentials and inducibility (negative predictive value = 91%; p = 0.03). No correlation was found between the ejection fraction, the grade of arrhythmia, the cardiopathy and inducibility. In patients with ischaemic cardiopathy, PVS has allowed to identify a subgroup of patients with high risk of sudden death. In this subgroup, serial PVS for drug testing has contributed to choose the therapeutic regimen supposed to be more effective for prevention of fatal arrhythmia. Multiple factors explain sudden death, even though the initial treatment has been chosen by electrophysiologic studies. For non inducible patients, empiric treatment is not proven to be reliable, and the best therapeutic regimen is still unidentified, especially in the subgroup of patients with low ejection fraction. In this subgroup, the implantable cardioverter defibrillator vives better protection against sudden rhythmic death.

Adolescent↗
PubMed2000

NMDA receptor activation in the aged rat hippocampus.

Age-related alterations of N-methyl-D-aspartate receptor (NMDAr) activation were investigated in the CA1 field of hippocampal slices from young (3-6 months old) and aged (25-33 months old) Sprague-Dawley rats by using ex vivo extracellular electrophysiological recording techniques. NMDAr-mediated field excitatory postsynaptic potentials (fEPSPs) were induced by electrical stimulation of glutamatergic fibers in a magnesium (Mg(2+))-free medium supplemented with the non-NMDAr antagonist CNQX. The fEPSPs were significantly smaller in aged rats, whereas the response of presynaptic afferent fibers remained unaffected. No significant age-related differences were found in the ability of Mg(2+) to depress the magnitude of NMDAr-mediated fEPSPs. The responsiveness of postsynaptic NMDAr to the agonist was assessed in both groups of animals. No age-related differences were recorded either in the depolarizing effect of bath-applied NMDA or in the magnitude of the depolarization after altering extracellular Mg(2+) concentration. Finally, short-term potentiation (STP) of excitatory transmission was studied in young and aged rats considering the pivotal role of NMDAr in synaptic plasticity. No age-related alterations of the magnitude and the time course of STP in response to 10 or 30Hz conditioning stimulation were found. Because of the decrease in the magnitude of NMDAr-mediated synaptic transmission in aged animals, the absence of obvious modifications of synaptic plasticity suggests the occurrence of compensatory mechanisms that are discussed.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Involvement of sst2 somatostatin receptor in locomotor, exploratory activity and emotional reactivity in mice.

Somatostatin (SRIF) controls many physiological and pathological processes in the central nervous system but the respective roles of the five receptor isotypes (sst1-5) that mediate its effects are yet to be defined. In the present study, we attempted to identify functions of the sst2 receptor using mice with no functional copy of this gene (sst2 KO mice). In contrast with control 129Sv/C57Bl6 mice, sst2 mRNA was no longer detectable in the brain of sst2 KO mice; 125I-labeled Tyr0DTrp8-SRIF14 binding was also greatly reduced in almost all brain structures except for the hippocampal CA1 area, demonstrating that sst2 accounts for most SRIF binding in mouse brain. Invalidation of this subtype generated an increased anxiety-related behaviour in a number of behavioural paradigms, while locomotor and exploratory activity was decreased in stress-inducing situations. No major motor defects could be detected. sst2 KO mice also displayed increased release of pituitary ACTH, a main regulator of the stress response. Thus, somatostatin, via sst2 receptor isotype pathways, appears involved in the modulation of locomotor, exploratory and emotional reactivity in mice.

Adrenocorticotropic Hormone↗
PubMed1999

Glutamatergic synaptic responses and long-term potentiation are impaired in the CA1 hippocampal area of calbindin D(28k)-deficient mice.

The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to glutamatergic neurotransmission and synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice, with the use of extracellular recordings in the ex vivo slice preparation. The amplitude of non-N-methyl-D-aspartate receptor (non-NMDAr)-mediated extracellular field excitatory postsynaptic potentials (fEPSPs) recorded in control medium was significantly greater in CaBP-deficient mice, whereas the afferent fiber volley was not affected. In contrast, the amplitude of NMDAr-mediated fEPSPs isolated in a magnesium-free medium after blockade of non-NMDAr and GABAergic receptors was significantly depressed in these animals. No alteration in the magnitude of paired-pulse facilitation was found, indicating that the presynaptic calcium mechanisms controlling glutamate release were not altered in CaBP-deficient mice. The magnitude and time course of the short-term potentiation (STP) of fEPSPs induced by a 30 Hz conditioning stimulation, which was blocked by the NMDAr antagonist 2-amino-5-phosphonovalerate acid (2-APV), was not impaired in the transgenic mice, whereas long-term potentiation (LTP) induced by a 100 Hz tetanus was not maintained. The long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 15 min) in the presence of the GABA antagonist bicuculline was not altered. These results argue for a contribution of CaBP to the mechanisms responsible for the maintenance of long-term synaptic potentiation, at least in part by modulating the activation of NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Protein tyrosine kinase inhibitors reduce high-voltage activating calcium currents in CA1 pyramidal neurones from rat hippocampal slices.

We have investigated the effects of protein tyrosine kinases (PTKs) inhibitors on high-threshold voltage activating (HVA) calcium currents in CA1 pyramidal neurones, whole-cell patch-clamp recorded from rat hippocampal slices. Genistein (100 microM) and tyrphostin B42 (100 microM), two PTKs inhibitors, reduced the steady-state barium current (IBa). On the other hand, daidzein and genistin (100 microM), two inactive analogues of genistein, had no effect on IBa amplitude. The inhibition induced by genistein was more pronounced at negative potentials. In order to characterize the calcium channels subtypes inhibited by PTKs inhibitors, we examined the effect of genistein in the presence of different calcium channel blockers. When L-type calcium channels were blocked by nifedipine, genistein induced a strong inhibition of the nifedipine-resistant IBa, suggesting an effect on non-L-type channels. Genistein did not antagonize the depressant effect of omega-Conotoxin-GVIA, a selective N-type calcium channel blocker, suggesting that N-type channels were not blocked by genistein. omega-Conotoxin-MVIIC (3-10 microM), a selective P/Q-type calcium channel blocker, greatly antagonized the depressant effect of genistein. Our results suggest that PTKs inhibitors reduce P-/Q-type, but not L- or N-types calcium currents in neurones of the CNS. The possible modulation of calcium channels by endogenous PTKs is discussed.

Animals↗
PubMed1997

Synaptic functions in the aged rat hippocampus: a target for corticosteroids?

The role of corticosteroids in brain aging remains a controversial issue. Conceivably, if corticosteroids levels are increased in the aged brain, neuronal function might be altered. For instance, GABA-mediated synaptic events, spike accommodation and afterhyperpolarizing potentials (AHPs) might be modified. Our electrophysiological results show that the most consistent alterations observed in the aged rat hippocampus concern cholinergic receptors, glutamatergic NMDA receptors and GABAB receptors mediated synaptic potentials. In contrast no consistent alterations were observed in afterhyperpolarizing potentials, calcium spikes, or GABAA mediated synaptic events. Therefore our electrophysiological results are difficult to reconcile with a 'glucocorticoid cascade hypothesis,' involving an elevated level of corticosterone in the aged rat.

Adrenal Cortex Hormones↗
PubMed1996

Synaptic mechanisms and calcium binding proteins in the aged rat brain.

Synaptic mechanisms were studied ex vivo in the aged rat hippocampus, using a slice preparation and intracellular electrophysiological recordings of the CA1 pyramidal neurons. A dramatic depression of the slow cholinergic excitatory postsynaptic potential (EPSP) and of the slow, GABAB-mediated inhibitory postsynaptic potential (IPSP) were observed. These age-related changes were consistently found in three different strains of rats. The mechanisms involve 1) changes in the properties of the postsynaptic muscarinic receptors, and possibly in acetylcholine release (for the postsynaptic muscarinic receptors, and possbily in acetylcholine release (for the cholinergic EPSP), and 2) alterations in the presynaptic GABAergic interneurons, as shown by a loss in calbindin immunoreactivity (for the GABAergic IPSP). The immunoreactivity for three calcium binding proteins (calbindin, parvalbumin and calretinin) was studied in the aged rat brain. Immunoreactivity for calbindin was dramatically reduced in the pyramidal neurons of the CA1 field and in a subpopulation of interneurons in the hippocampus. Immunoreactivity for parvalbumin was reduced in the medial septal area, and in the cingulate cortex, whereas no change was observed for calretinin. These age-related alterations could 1) modify the functions of the hippocampal networks, and possibly contribute to the age-related cognitive deficits, and 2) compromise intraneuronal calcium buffering, and thus make neurons more vulnerable to toxic insults.

Animals↗
PubMed1996

Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices.

The effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, memantine (1-amino-3,5-dimethyladamantane) and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten-5,10-imin e maleate) were compared on synaptic transmission and long-term potentiation (LTP) in hippocampal slices and on NMDA-induced currents in cultured superior collicular neurones. 2. Memantine (10-100 microM) reversibly reduced, but did not abolish, NMDA receptor-mediated secondary population spikes recorded in area CA1 of hippocampal slices bathed in Mg(2+)-free artificial cerebrospinal fluid. 3. Memantine (100 microM) antagonized NMDA receptor-mediated excitatory postsynaptic currents recorded in area CA1 in a strongly voltage-dependent manner i.e. depressed to 11 +/- 4% of control at -35 mV and 95 +/- 5% of control at +40 mV (n = 9), with no apparent effect on response kinetics. 4. The effects of MK-801 and memantine on the induction of LTP were assessed after prolonged pre-incubations with these antagonists. When present for 6.6 +/- 0.4 h prior to tetanic stimulation, memantine blocked the induction of LTP with an IC50 of 11.6 +/- 0.53 microM. By comparison, similar long pre-incubations with MK-801 (6.4 +/- 0.4 h) blocked the induction of LTP with an IC50 of 0.13 +/- 0.02 microM. 5. Memantine and MK-801 reduced NMDA-induced currents in cultured superior colliculus neurones recorded at -70 mV with IC50s of 2.2 +/- 0.2 microM and 0.14 +/- 0.04 microM respectively. The effects of memantine were highly voltage-dependent and behaved as though the affinity decreased epsilon fold per 50 mV of depolarization (apparent delta = 0.71). In contrast, under the conditions used, MK-801 appeared to be much less voltage-dependent i.e. affinity decreased epsilon fold per 329 mV of depolarization (apparent delta = 0.15). 6. Depolarizing steps from -70 mV to +50 mV in the continuous presence of memantine (10 microM) caused a rapid relief of blockade of NMDA-induced currents from 83.7 +/- 1.9% to 21.8 +/- 1.8% (n = 5). This relief was best fitted by a double exponential function (17.2 +/- 11.7 and 698 +/- 204 ms), the faster component of which was most pronounced. 7. In conclusion, whereas MK-801 is equipotent in blocking NMDA-induced currents (at - 70 mV) and the induction of LTP, memantine is relatively less potent in blocking the induction of LTP. This is due to its rapid relief of blockade upon depolarization; a property which might explain its promising clinical profile in the treatment of chronic neurodegenerative diseases.

Action Potentials↗
PubMed1995

Genomic clones encoding 11S globulins in oats (Avena sativa L.).

We have isolated two complete genomic clones, Glav1 and Glav3, encoding 11S globulins (legumins) in oat. The structure of Glav1 deviates from that of the typical legumin gene. This clone possesses an extra intron and an extra exon that is composed entirely of repeats of sequences found elsewhere in the clone. If this exon is functional, the protein encoded by Glav1 will contain novel octapeptide and hendecapeptide repeats. The two Glav clones show stronger and more extensive homology with one another than with the two previously published genomic clones, OG1-E1 and ASglob5. This result suggests that the oat globulin gene family may be divided into distinct subfamilies or that there may be significant cultivar-specific differences among members of this gene family.

Amino Acid Sequence↗
PubMed1994

Loss of calbindin-immunoreactivity in CA1 hippocampal stratum radiatum and stratum lacunosum-moleculare interneurons in the aged rat.

Alterations in hippocampal circuitry may underly age-related learning and memory impairment. We showed in a previous study that the GABAB-mediated slow inhibitory postsynaptic potential (IPSP) induced in CA1 pyramidal neurons by electrical stimulation of stratum radiatum, is depressed in the hippocampus of the aged rat. This could be due to alterations in GABAergic interneuron functions. We report in this study that the number of hippocampal calbindin-immunoreactive (CaBP-IR) GABAergic interneurons is decreased in the aged rat. The mean number of CaBP-IR interneurons per slice decreases by 50% in the aged rat. The most severe loss was observed in the stratum radiatum of CA1 (78%), with a less consistent loss of immunoreactivity in CA3 (35%). In contrast, the mean number of interneurons containing parvalbumin (PV), was not significantly decreased in the aged rat. Our results show a loss of CaBP immunoreactivity in a population of GABAergic interneurons, which might be related to an altered function of these interneurons and consequently of GABAergic synaptic transmission in the aged rat. In contrast, PV immunoreactivity in interneurons located close to the pyramidal layer does not decrease in the hippocampus of the aged rat.

Aging↗
PubMed1994

The nitric oxide--cyclic GMP pathway and synaptic depression in rat hippocampal slices.

The ability of exogenous nitric oxide (NO) to modify synaptic transmission was investigated in area CA1 of the rat hippocampal slice. The NO donors S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (SNOG) depressed field excitatory postsynaptic potentials evoked by low frequency stimulation of the Schaffer collateral-commissural pathway. Upon washout of the NO donors, synaptic transmission rapidly returned to control levels. A similar reversible synaptic depression was produced by SNAP when tetanic stimulation (100 Hz; 1 s) was delivered in its presence. The effect of SNAP was not mimicked by its precursor or breakdown product and was blocked by haemoglobin, indicating that the effect involved NO. Roussin's black salt, a photolabile NO donor, also depressed transiently field excitatory postsynaptic potentials following photolysis. The depression was induced rapidly following a flash of UV light (20 s duration) focused onto the slice using a confocal microscope. The depressant effect of the NO donors on synaptic transmission was mimicked by zaprinast, a specific cGMP-phosphodiesterase inhibitor. Zaprinast depressed to a similar extent both the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptor-mediated components of excitatory postsynaptic currents without affecting passive membrane properties, indicating a presynaptic locus of action. SNAP, SNOG and zaprinast all elevated cGMP levels in rat hippocampal slices. Immunocytochemical staining revealed that the cGMP accumulation was mainly in a network of varicose fibres running throughout the CA1 region, consistent with a presynaptic site of action of NO. We conclude that NO, possibly through activation of guanylate cyclase, may be involved in transient presynaptic depression in the CA1 region of the hippocampus.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

[Aging of memory mechanisms].

Human amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age-related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1993

Cholinergic and non-cholinergic synaptic mechanisms in the aged rat hippocampus.

We compared age-related alterations in the electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons in three strains of rats (Sprague-Dawley, Fisher 344 and Wistar) at 3-4 and 25-32 months of age, using the in vitro slice preparation. The most consistent age-related alterations were: a decrease in membrane excitability, a decrease in the amplitude and duration of inhibitory postsynaptic potentials and a decreased sensitivity to the effect of the cholinergic agonist carbachol. In contrast, no consistent alterations in calcium-dependent events were observed in these strains of rats. The age-related changes in the duration of the after-hyperpolarization (AHP) were different (and even opposite) depending on the strain studied. Our results show that age-related changes observed in a given strain are not necessarily present in all strains of the same species.

Aging↗
PubMed1993

Different effects of omega-conotoxin GVIA at excitatory and inhibitory synapses in rat CA1 hippocampal neurons.

The nature of the coupling mechanism of presynaptic calcium channels involved in the release of neurotransmitters in the mammalian central nervous system is unknown. Using intracellular recordings from CA1 neurons in the rat hippocampal slice preparation, we show that the N-type calcium channels antagonist omega-conotoxin GVIA (omega-CgTx) blocks partially the excitatory (EPSP) and totally the inhibitory (IPSP) synaptic transmission in CA1 hippocampal pyramidal neurons. In addition, the inhibitory effect of omega-CgTx on IPSPs is strongly depressed by intrahippocampal injection of PTX, while the effect on EPSP is not. The results suggest that the nature or the regulation of calcium channels might be different, depending on the location of these channels on excitatory or inhibitory terminals.

2-Amino-5-phosphonovalerate↗
PubMed1993

Presynaptic inhibitory effect of baclofen on hippocampal inhibitory synaptic transmission involves a pertussis toxin-sensitive G-protein.

The involvement of a pertussis toxin (PTX)-sensitive G-protein in the activation of presynaptic GABAB receptor is controversial. In the present study, we reinvestigated the problem using intracellular recordings from CA1 neurons in rat hippocampus slices. We showed that the presynaptic inhibitory effect of baclofen is mediated differently at excitatory and inhibitory synapses. Excitatory (e.p.s.p.) and inhibitory (i.p.s.p.) postsynaptic potentials were strongly antagonized by baclofen in control rats. Three days after administration of PTX into the stratum radiatum of the hippocampus, the inhibitory effect of baclofen on i.p.s.p. was antagonized. In contrast, the inhibitory effect on e.p.s.p. was partly maintained. These results suggest that different sub-types of GABAB receptors exist on nerve terminals with different transduction mechanisms. GABAB receptors located on GABAergic inhibitory terminals are linked to a PTX-sensitive G-protein, whereas those located on excitatory terminals could consist of a PTX-sensitive type and a PTX-insensitive type. In addition, we showed that part of the inhibitory effect of baclofen at excitatory synapses is independent of omega-conotoxin (omega-CgTx)-sensitive N-type Ca2+ channels.

Animals↗