Jean‐Pierre Mothet

CentraleSupélec

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Loredano Pollegioni

University of Insubria

Magalie Martineau

Inserm

Stéphane H. R. Oliet

Neurocentre Magendie

Silvia Sacchi

University of Insubria

Glenn Dallérac

Centre National de la Recherche Scientifique

L Tauc

Laboratoire de Neurobiologie Cellulaire et Moléculaire

G. Baux

Laboratoire de Neurobiologie Cellulaire et Moléculaire

P. Fossier

Institut des Neurosciences Paris-Saclay

Fabrice Turpin

University of Queensland

Jérôme Dulong

Université de Bordeaux

Cooperative Institutions

Centre National de la Recherche Scientifique

128

Inserm

117

Université Paris Cité

Université de Bordeaux

University of Lausanne

Sorbonne Université

Aix-Marseille Université

Centre de Recherche en Neurobiologie - Neurophysiologie de Marseille

Laboratoire de Neurobiologie Cellulaire et Moléculaire

Neurocentre Magendie

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Opposite effects of nitric oxide on identified inhibitory and excitatory cholinergic synapses of Aplysia californica.

PubMed (1996)

Jean‐Pierre Mothet P. Fossier A. Schirar L Tauc G. Baux

The effects of nitric oxide on evoked acetylcholine (ACh) release were studied at two identified cholinergic neuro-neuronal synapses of the nervous system of the mollusc Aplysia californica. The NO-donor, 3-morpholinosydnonimine (SIN-1), decreased the amplitude of evoked inhibitory postsynaptic currents (buccal ganglion) and potentiated that of evoked excitatory postsynaptic currents (abdominal ganglion). SIN-1 acted by modulating the number of ACh quanta released. 8Br-cGMP mimicked the effects of NO on ACh release in both types of synapses thus pointing to the involvement of a NO-sensitive guanylate cyclase. Presynaptic voltage-dependent Ca2+ and K+ (IA and late outward rectifier) currents were not modified by SIN-1 suggesting another final target for NO/cGMP. The labelling of a NO-synthase by immunostaining in several neurones as well as the modulation of ACh release by L-arginine indicate that an endogenous NO-synthase is involved in the modulation of synaptic efficacy in both buccal and abdominal ganglia.

Aplysia

Postsynaptic Current

Source

Cite

Citations (9)

A nitric oxide synthase activity is involved in the modulation of acetylcholine release inAplysia ganglion neurons: A histological, voltammetric and electrophysiological study

Neuroscience (1995)

A. Meulemans Jean‐Pierre Mothet A. Schirar P. Fossier L Tauc

10.1016/0306-4522(95)00316-b

Cite

Citations (48)

Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments

Molecular Psychiatry (2018)

Francesco Petrelli Glenn Dallérac Luca Pucci Corrado Calì Tamara Zehnder

Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders.

Homeostasis

10.1038/s41380-018-0226-y

Cite

Citations (98)

Confocal imaging and tracking of the exocytotic routes for D‐serine‐mediated gliotransmission

Glia (2008)

Magalie Martineau Thierry Galli Gérard Baux Jean‐Pierre Mothet

D-Serine is an astrocyte-derived regulator for N-methyl-D-aspartate receptors, but the intracellular routes of its trafficking are still largely unknown. Here, we combined confocal microscopy with colocalization quantification to track the astrocytic organelles that store D-serine. We report that D-serine colocalizes with the transfected eGFP-synaptobrevin/VAMP2 and eGFP-cellubrevin/VAMP3, two v-SNAREs of the regulated secretory pathway. No significant colocalization was found with markers of the endosomal sorting and recycling system: EEA1, eGFP-endobrevin/VAMP8, eGFP-TI-VAMP/VAMP7, LAMP1, and CD63. Blockade of vesicular budding with colchicine shows that secretory vesicles import D-serine downstream to the Golgi apparatus. Finally, treatment of astrocytes with the Ca2+-ionophore A23187, glutamate agonists, or bradykinin trigger translocation of synaptobrevin/VAMP2 to the plasma membrane with a concomitant disappearance of D-serine from the regulated secretory pathway. Our results provide morphological evidence for a vesicular storage of D-serine in the regulated secretory pathway and the possible recruitment of these stores by Ca2+ mobilization to release D-serine.

Colocalization

Synaptobrevin

10.1002/glia.20696

Cite

Citations (106)

Purification of serine racemase: ) neuromodulator D-serine

Herman Wolosker Kevin N. Sheth Masaaki Takaha Christopher D. Ferris Solomon H. Snyder

High levels of D-serine occur in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-D-aspartate receptors. In glial cul- tures of rat cerebral cortex, D-serine is enriched in type II astrocytes and is released upon stimulation with agonists of non-N-methyl-D-aspartate glutamate receptors. The high lev- els of D-serine in discrete areas of rat brain imply the existence of a biosynthetic pathway. We have purified from rat brain a soluble enzyme that catalyzes the direct racemization of L-serine to D-serine. Purified serine racemase has a molecular mass of 37 kDa and requires pyridoxal 5'-phosphate for its activity. The enzyme is highly selective toward L-serine, failing to racemize any other amino acid tested. Properties such as pH optimum, Km values, and the requirement for pyridoxal phos- phate resemble those of bacterial racemases, suggesting that the biosynthetic pathway for D-amino acids is conserved from bacteria to mammalian brain.

Pyridoxal phosphate

Source

Cite

Citations (0)

Opposite actions of nitric oxide on cholinergic synapses: which pathways?

Proceedings of the National Academy of Sciences (1996)

Jean‐Pierre Mothet P. Fossier L Tauc G. Baux

Nitric oxide (NO) produced opposite effects on acetylcholine (ACh) release in identified neuroneuronal Aplysia synapses depending on the excitatory or the inhibitory nature of the synapse. Extracellular application of the NO donor, SIN-1, depressed the inhibitory postsynaptic currents (IPSCs) and enhanced the excitatory postsynaptic currents (EPSCs) evoked by presynaptic action potentials (1/60 Hz). Application of a membrane-permeant cGMP analog mimicked the effect of SIN-1 suggesting the participation of guanylate cyclase in the NO pathway. The guanylate cyclase inhibitor, methylene blue, blocked the NO-induced enhancement of EPSCs but only reduced the inhibition of IPSCs indicating that an additional mechanism participates to the depression of synaptic transmission by NO. Using nicotinamide, an inhibitor of ADP-ribosylation, we found that the NO-induced depression of ACh release on the inhibitory synapse also involves ADP-ribosylation mechanism(s). Furthermore, application of SIN-1 paired with cGMP-dependent protein kinase (cGMP-PK) inhibitors showed that cGMP-PK could play a role in the potentiating but not in the depressing effect of NO on ACh release. Increasing the frequency of stimulation of the presynaptic neuron from 1/60 Hz to 0.25 or 1 Hz potentiated the EPSCs and reduced the IPSCs. In these conditions, the potentiating effect of NO on the excitatory synapse was reduced, whereas its depressing effect on the inhibitory synapse was unaffected. Moreover the frequency-dependent enhancement of ACh release in the excitatory synapse was greatly reduced by the inhibition of NO synthase. Our results indicate that NO may be involved in different ways of modulation of synaptic transmission depending on the type of the synapse including synaptic plasticity.

Postsynaptic Current

Excitatory synapse

10.1073/pnas.93.16.8721

Cite

Citations (39)

Excitatory drive of cortical fast-spiking GABAergic interneurons is set by D-serine acting on NMDA receptors

Research Square (Research Square) (2022)

Pierre Lecouflet Steeve Maldera Brigitte Potier Loredano Pollegioni Jean‐Pierre Mothet

Abstract N-methyl-D-aspartate receptors (NMDARs) populate GABAergic interneurons, where they play a critical role in shaping circuit motifs and memory. However, we are largely ignoring whether and how NMDARs at GABAergic interneurons are gated by signals released in their surrounding microenvironment. Here we explore the dynamics of the co-agonist site occupancy by D-serine and glycine at glutamatergic synapses onto parvalbumin positive GABAergic interneurons in the adolescent prefrontal cortex, an area central to complex cognitive operation. We discovered that D-serine but not glycine is required for maintaining the activity of NMDAR at the GABAergic interneurons and that the identity of the co-agonist is not determined by the synaptic regime. Our study extends the physiological implications of D-serine in brain physiopathology by uncovering its control of inhibitory synaptic networks through NMDARs.

Interneuron

10.21203/rs.3.rs-1323674/v1

Cite

Citations (0)

Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels in hippocampal astrocytes

Glia (2015)

Verónica Abudara Lisa Roux Glenn Dallérac Isabel Matias Jérôme Dulong

Glia plays an active role in neuronal functions and dysfunctions, some of which depend on the expression of astrocyte connexins, the gap junction channel and hemichannel proteins. Under neuroinflammation triggered by the endotoxin lipopolysacharide (LPS), microglia is primary stimulated and releases proinflammatory agents affecting astrocytes and neurons. Here, we investigate the effects of such microglial activation on astrocyte connexin‐based channel functions and their consequences on synaptic activity in an ex vivo model. We found that LPS induces astroglial hemichannel opening in acute hippocampal slices while no change is observed in gap junctional communication. Based on pharmacological and genetic approaches we found that the LPS‐induced hemichannel opening is mainly due to Cx43 hemichannel activity. This process primarily requires a microglial stimulation resulting in the release of at least two proinflammatory cytokines, IL‐1β and TNF‐α. Consequences of the hemichannel‐mediated increase in membrane permeability are a calcium rise in astrocytes and an enhanced glutamate release associated to a reduction in excitatory synaptic activity of pyramidal neurons in response to Schaffer's collateral stimulation. As a whole our findings point out astroglial hemichannels as key determinants of the impairment of synaptic transmission during neuroinflammation. GLIA 2015;63:795–811

Pannexin

Proinflammatory cytokine

Neuroglia

10.1002/glia.22785

Cite

Citations (114)

Regulation of N-methyl-d-aspartate receptors by astrocytic d-serine

Neuroscience (2008)

Stéphane H. R. Oliet Jean‐Pierre Mothet

Excitotoxicity

Long-term depression

10.1016/j.neuroscience.2008.01.071