Biomedical subjects

Alain Marty

Publications and source records attributed to Alain Marty.

13 recordsLinked to original sources

PubMed2006

High-Curie-temperature ferromagnetism in self-organized Ge1-xMnx nanocolumns.

The emerging field of spintronics would be dramatically boosted if room-temperature ferromagnetism could be added to semiconductor nanostructures that are compatible with silicon technology. Here, we report a high-TC (>400K) ferromagnetic phase of (Ge,Mn) epitaxial layer. The manganese content is 6%, and careful structural and chemical analyses show that the Mn distribution is strongly inhomogeneous: we observe eutectoid growth of well-defined Mn-rich nanocolumns surrounded by a Mn-poor matrix. The average diameter of these nanocolumns is 3nm and their spacing is 10nm. Their composition is close to Ge(2)Mn, which corresponds to an unknown germanium-rich phase, and they have a uniaxially elongated diamond structure. Their Curie temperature is higher than 400K. Magnetotransport reveals a pronounced anomalous Hall effect up to room temperature. A giant positive magnetoresistance is measured from 7,000% at 30K to 200% at 300K and 9T, with no evidence of saturation.

Journal Article↗

PubMed2005

Control of interneurone firing pattern by axonal autoreceptors in the juvenile rat cerebellum.

Recent work has shown that certain neurones have axonal GABA(A) receptors, whose tonic activation modifies their firing properties and neurotransmitter release capability. In addition, results obtained in interneurones of the molecular layer of the cerebellum indicate that action potential-released GABA binds back to the axon that released it, generating an autoreceptor current. In the present paper, we show that at physiological Cl(i)- concentration (15 mm) and at 34-36 degrees C, the autoreceptor current generates a large amplitude (up to 21 mV) after depolarization that lasts for about 150 ms, and that occasionally leads to double firing. Furthermore we show that elimination of the after depolarization, by either blocking GABA(A) receptors, or eliminating the autoreceptor currents through prolonged whole-cell recording, decreases burst firing. I(h) (a hyperpolarization-activated current) was previously found to be prominent in interneurone axons. We show that blocking I(h) leads to an increase in the amplitude of the autoreceptor current as well as of the associated after depolarization, suggesting a shunting effect of I(h) on autoreceptor-mediated after depolarization. Conversely, blocking I(h) accentuates burst firing. The effects of autoreceptor-mediated after depolarization on firing are prominent during a period of development when interneurone synapses are stabilized and vanish by postnatal day 17 (PN 17), together with the expression of the autoreceptor current. Altogether, this work reveals a new role for autoreceptors in the regulation of cell excitability and firing pattern, which may contribute to the development and stabilization of the cerebellar network.

Action Potentials↗

PubMed2005

Developmental changes in parvalbumin regulate presynaptic Ca2+ signaling.

Certain interneurons contain large concentrations of specific Ca2+-binding proteins (CBPs), but consequences on presynaptic Ca2+ signaling are poorly understood. Here we show that expression of the slow CBP parvalbumin (PV) in cerebellar interneurons is cell specific and developmentally regulated, leading to characteristic changes in presynaptic Ca2+ dynamics (Ca(i)). Using whole-cell recording and fluorescence imaging, we studied action potential-evoked Ca(i) transients in axons of GABA-releasing interneurons from mouse cerebellum. At early developmental stages [postnatal days 10-12 (P10-P12)], decay kinetics were significantly faster for basket cells than for stellate cells, whereas at P19-P21 both interneurons displayed fast decay kinetics. Biochemical and immunocytochemical analysis showed parallel changes in the expression levels and cellular distribution of PV. By comparing wild-type and PV(-/-) mice, PV was shown to accelerate the initial decay of action potential-evoked Ca(i) signals in single varicosities and to introduce an additional slow phase that summates during bursts of action potentials. The fast initial Ca(i) decay accounts for a previous report that PV elimination favors synaptic facilitation. The slow decay component is responsible for a pronounced, PV-dependent, delayed transmitter release that we describe here at interneuron-interneuron synapses after presynaptic bursts of action potentials. Numerical simulations account for the effect of PV on Ca(i) kinetics, allow estimates for the axonal PV concentration (approximately 150 microm), and predict the time course of volume-averaged Ca(i) in the absence of exogenous buffer. Overall, PV arises as a major contributor to presynaptic Ca(i) signals and synaptic integration in the cerebellar cortex.

Action Potentials↗

PubMed2005

Presynaptic calcium stores and synaptic transmission.

Following the gradual recognition of the importance of intracellular calcium stores for somatodendritic signaling in the mammalian brain, recent reports have also indicated a significant role of presynaptic calcium stores. Ryanodine-sensitive stores generate local, random calcium signals that shape spontaneous transmitter release. They amplify spike-driven calcium signals in presynaptic terminals, and consequently enhance the efficacy of transmitter release. They appear to be recruited by an association with certain types of calcium-permeant ion channels, and they induce specific forms of synaptic plasticity. Recent research also indicates a role of inositoltrisphosphate-sensitive presynaptic calcium stores in synaptic plasticity.

Animals↗

PubMed2005

Excitatory effects of GABA in established brain networks.

Although GABA remains the predominant inhibitory neurotransmitter of the brain, there are numerous recent examples of excitatory actions of GABA. These actions can be classified in two broad categories: phasic excitatory effects, as follow single activation of GABAergic afferents, and sustained excitatory effects, as follow prolonged activation of GABA(A) receptors. Evidence reviewed here indicates that, contrary to common belief, these effects are not restricted to embryonic or neonatal preparations.

Animals↗

PubMed2004

Osmotic tension as a possible link between GABA(A) receptor activation and intracellular calcium elevation.

Intracellular calcium concentration rises have been reported following activation of GABA(A) receptors in neonatal preparations and attributed to activation of voltage-dependent Ca(2+) channels. However, we show that, in cerebellar interneurons, GABA(A) agonists induce a somatodendritic Ca(2+) rise that persists at least until postnatal day 20 and is not mediated by depolarization-induced Ca(2+) entry. A local Ca(2+) elevation can likewise be elicited by repetitive stimulation of presynaptic GABAergic afferent fibers. We find that, following GABA(A) receptor activation, bicarbonate-induced Cl(-) entry leads to cell depolarization, Cl(-) accumulation, and osmotic tension. We propose that this tension induces the intracellular Ca(2+) rise as part of a regulatory volume decrease reaction. This mechanism introduces an unexpected link between activation of GABA(A) receptors and intracellular Ca(2+) elevation, which could contribute to activity-driven synaptic plasticity.

Animals↗

PubMed2004

Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE).

Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE) are two related forms of short-term synaptic plasticity of GABAergic and glutamatergic transmission, respectively. They are induced by calcium concentration increases in postsynaptic cells and are mediated by the release of a retrograde messenger, which reversibly inhibits afferent synapses via presynaptic mechanisms. We review here: 1. The evidence accumulated during the 1990s that has led to the conclusion that DSI/DSE rely on retrograde signaling. 2. The more recent research that has led to the identification of endocannabinoids as the retrograde messengers responsible for DSI/DSE. 3. The possible mechanisms by which presynaptic type 1 cannabinoid receptors reduce synaptic efficacy during DSI/DSE. 4. The possible modes of induction of DSI/DSE by physiological activity patterns, and the partially conflicting evaluations of the calcium concentration increases required for cannabinoid synthesis. 5. Finally, the relation between DSI/DSE and other forms of long- and short-term synaptic inhibition, which were more recently associated with the production of endocannabinoids by postsynaptic cells. We conclude that recent studies on DSI/DSE have uncovered a specific and original mode of action for endocannabinoids in the brain, and that they have opened new avenues to understand the role of retrograde signaling in central synapses.

Animals↗

PubMed2003

Presynaptic ryanodine-sensitive calcium stores contribute to evoked neurotransmitter release at the basket cell-Purkinje cell synapse.

Presynaptic terminals of cerebellar basket cells are known to contain ryanodine-sensitive calcium stores (RyCSs); recently, it has been shown that these stores control the frequency of miniature synaptic currents in the absence of presynaptic spiking. Here, using paired recordings of basket cell-Purkinje cell synapses, we show that blocking the RyCSs with high concentration of ryanodine decreases the mean amplitude of evoked IPSCs to 70% of the control value. The paired-pulse ratio and failure rate increase, indicating that the reduction stems from a decreased probability of evoked neurotransmitter release. Various control experiments eliminate the possibility of an indirect effect of ryanodine via activation of postsynaptic receptors. Prolonged application of cyclopiazonic acid, a blocker of the endoplasmic reticulum calcium pump, totally abolishes the ryanodine action. Our results indicate that calcium released from presynaptic RyCSs enhances the amplitude of evoked GABAergic synaptic currents. The precise mechanism by which calcium released from internal stores affect action potential-dependent release is unknown; however, our results suggest that these stores do not provide additional calcium for each presynaptic action potential; rather, they appear to enhance depolarization-induced calcium signals indirectly, perhaps by increasing the basal level of cytosolic calcium concentration in the vicinity of release sites.

Animals↗

PubMed2003

Characterization of depolarization-induced suppression of inhibition using paired interneuron--Purkinje cell recordings.

Depolarization-induced suppression of inhibition (DSI) is a retrograde form of synaptic inhibition involving the Ca2+-dependent release of cannabinoids from the postsynaptic cell. DSI exerts multiple effects on presynaptic neurons: here, we establish the breakdown of DSI in its individual components at the synapses between basket and stellate cells and Purkinje cells. In the presence of tetrodotoxin, the change in IPSC frequency entirely accounted for the decrease of transmission during DSI; in contrast, without tetrodotoxin, the reductions of frequency and average amplitude gave equal contributions. In paired recordings, transmission displayed an irreversible rundown unless interneurons were recorded from with the perforated patch method. Under these conditions, a DSI of 68.8% was measured; the failure rate and the paired pulse ratio (at 20 msec intervals) increased from 1.2 to 20.2 and 95.6 to 132.6%, respectively, and the variance to mean ratio augmented 2.17-fold. Presynaptic dialysis with Cs+ led to a major potentiation of synaptic strength and to a marked reduction of DSI with respect to control potassium conditions; DSI recovered only partially when decreasing the extracellular Ca2+ concentration to match the control IPSC amplitudes. These results, combined with those of Kreitzer et al. (2002), indicate that three distinct presynaptic processes contribute to DSI: reductions of miniature frequency (13.4% of total DSI), of presynaptic action potential frequency (23.2%), and of the probability that presynaptic depolarizations elicit transmitter release (63.4%). The latter component involves a modulation of K+ channels and trial-to-trial modifications of the presynaptic signal.

Analysis of Variance↗

PubMed2003

Economically pertinent continuous amide formation by direct lipase-catalyzed amidation with ammonia.

An economically pertinent process for the lipase-catalyzed synthesis of amides was developed. A continuous plug flow reactor was used. The model reaction was the production of oleamide, a lubricant and anti-slip agent, via direct Candida antarctica lipase B-catalyzed amidation of oleic acid with ammonia. Of all solvents tested, 2-methyl-2-butanol was found to respond optimally to the demands formulated in our specifications. A continuous conversion of oleic acid into oleamide of 85% was obtained. A productivity of 4.5 tons oleamide per kg of enzyme per year was calculated, indicating a contribution of enzyme to the product price of only 4%. The volumetric productivity, 100 g. L(-1). h(-1), is 4 to 100 times higher than in literature procedures. A simple crystallization procedure leads to 99% purity.

Amides↗

PubMed2003

Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network.

Functional GABA synapses are usually assumed to be inhibitory. However, we show here that inhibitory and excitatory GABA connections coexist in the cerebellar interneuron network. The reversal potential of GABAergic currents (E(GABA)) measured in interneurons is relatively depolarized and contrasts with the hyperpolarized value found in Purkinje cells (-58 and -85 mV respectively). This finding is not correlated to a specific developmental stage and is maintained in the adult animal. E(GABA) in interneurons is close to the mean membrane potential (-56.5 mV, as measured with a novel "equal firing potential" method), and both parameters vary enough among cells so that the driving force for GABA currents can be either inward or outward. Indeed, using noninvasive cell-attached recordings, we demonstrate inhibitory, excitatory, and sequential inhibitory and excitatory responses to interneuron stimulation [results obtained both in juvenile (postnatal days 12-14) and subadult (postnatal days 20-25) animals]. In hyperpolarized cells, single synaptic GABA currents can trigger spikes or trains of spikes, and subthreshold stimulations enhance the responsiveness to subsequent excitatory stimulation over at least 30 msec. We suggest that the coexistence of excitatory and inhibitory GABA synapses could either buffer the mean firing rate of the interneuron network or introduce different types of correlation between neighboring interneurons, or both.

Action Potentials↗

PubMed2002

Efficient lipase catalysed production of a lubricant and surfactant formulation using a continuous solvent-free process.

The transesterification of sunflower oil with a high oleic acid residue content (typically 83.5%) with butanol-1 by immobilised Lipozyme was carried out in a solvent free system and in a continuous way. During the first 6 h of reactor operation, a transition phase was observed, in which the main products were butyl ester and glycerol. This latter being insoluble in the reaction mixture, it is adsorbed onto the enzyme support thus leading to a decrease in enzyme performance. Step by step, less and less glycerol is produced and finally when glycerol is no longer produced a steady state is attained. The product composition is a mixture of butyl ester (65 molar%), monoglyceride (26 molar%), diglyceride (6 molar%) and residual triglyceride (3 molar%). This mixture has interesting lubricant and surfactant properties. The reactor was maintained without any loss in activity for a period of 3 months. This result is very different to that obtained using an organic solvent (n-hexane) which leads to a total loss of enzyme activity within a few hours.

Bioreactors↗

PubMed2002

Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids.

Depolarization-induced suppression of inhibition (DSI) is a form of short-term plasticity of GABAergic synaptic transmission that is found in cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. DSI involves the release of a calcium-dependent retrograde messenger by the somatodendritic compartment of the postsynaptic cell. Both glutamate and endogenous cannabinoids have been proposed as retrograde messenger. Here we show that, in cerebellar parasagittal slices, type 1 cannabinoid receptors (CB1Rs) are expressed at high levels in axons of GABAergic interneurons and in presynaptic terminals onto Purkinje cells. Application of the cannabinoid antagonist AM-251 (500 nm) leads to the abolition of the DSI of evoked currents (eIPSCs) recorded in paired recordings and to a strong reduction of the DSI of TTX-insensitive miniature events (mIPSCs) recorded from Purkinje cells. Furthermore, the CB1R agonist WIN 55-212,2 (5 microm) induces a presynaptic inhibition of synaptic currents similar to that occurring during DSI, as well as an occlusion of DSI after stimulation of Purkinje cells. Moreover, WIN 55-212,2 reduces the calcium transients evoked in presumed presynaptic varicosities by short trains of action potentials. Our results indicate that DSI is mediated by the activation of presynaptic CB1Rs and that an endogenous cannabinoid is a likely candidate retrograde messenger in this preparation. They further suggest that DSI involves distinct presynaptic modifications for eIPSCs and mIPSCs, including an inhibition of action potential-evoked calcium rises.

Action Potentials↗