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2. Endogenous cannabinoids in the piriform cortex tune olfactory perception

Author

Geoffrey Terral, Evan Harrell, Gabriel Lepousez, Yohan Wards, Dinghuang Huang, Tiphaine Dolique, Giulio Casali, Antoine Nissant, Pierre-Marie Lledo, Guillaume Ferreira, Giovanni Marsicano, and Lisa Roux

Subjects
Science
Abstract

Abstract Sensory perception depends on interactions between external inputs transduced by peripheral sensory organs and internal network dynamics generated by central neuronal circuits. In the sensory cortex, desynchronized network states associate with high signal-to-noise ratio stimulus-evoked responses and heightened perception. Cannabinoid-type-1-receptors (CB1Rs) - which influence network coordination in the hippocampus - are present in anterior piriform cortex (aPC), a sensory paleocortex supporting olfactory perception. Yet, how CB1Rs shape aPC network activity and affect odor perception is unknown. Using pharmacological manipulations coupled with multi-electrode recordings or fiber photometry in the aPC of freely moving male mice, we show that systemic CB1R blockade as well as local drug infusion increases the amplitude of gamma oscillations in aPC, while simultaneously reducing the occurrence of synchronized population events involving aPC excitatory neurons. In animals exposed to odor sources, blockade of CB1Rs reduces correlation among aPC excitatory units and lowers behavioral olfactory detection thresholds. These results suggest that endogenous endocannabinoid signaling promotes synchronized population events and dampen gamma oscillations in the aPC which results in a reduced sensitivity to external sensory inputs.

Published
2024
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3. Long-range GABAergic projections contribute to cortical feedback control of sensory processing

Author

Camille Mazo, Antoine Nissant, Soham Saha, Enzo Peroni, Pierre-Marie Lledo, and Gabriel Lepousez

Subjects
Science
Abstract

Classically, corticofugal feedback projections that adjust sensory processing are excitatory. Here, the authors uncover the presence of top-down inhibitory projections from cortical GABAergic neurons in the olfactory system, which directly inhibit olfactory bulb circuits.

Published
2022
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6. C

Author

Davis, Justin R., Giles, Andrew C., Rankin, Catharine H., Bell, Jonathan, Kimura, Hiroshi, Uemura, Tadashi, Kidokoro, Yoshi, Lemieux, Mado, Koninck, Paul De, Carbone, Emilio, Senatore, Adriano, Spafford, J. David, Dowie, Megan J., Grimsey, Natasha L., Glass, Michelle, Gillis, Kevin D., Hunter, Peter, Budgell, Brian, Roy, Arijit, Wilson, Richard J. A., Hikosaka, Okihide, Esfeld, Michael, Harbecke, Jens, Mitsuhashi, Takayuki, Takahashi, Takao, Kageyama, Ryoichiro, Ohsawa, Ryosuke, Ohtsuka, Toshiyuki, Lalley, Peter M., Nitabach, Michael N., Paton, Julian F. R., Waitzman, David M., Nattie, Eugene, Li, Aihua, Tsunoda, Ikuo, Kobayashi-Warren, Mikako, Libbey, Jane E., Fujinami, Robert S., Kulkarni, Amod P., Kellaway, Laurie A., Kotwal, Girish J., Morgen, Katrin E., Ciufolini, Maria Grazia, Nicoletti, Loredana, Davis, Randall L., Hofer, Markus J., Campbell, Iain L., Jensen, Troels S., Finnerup, Nanna B., Straub, Volko A., Benarroch, Eduardo E., Bronstein, Adolfo M., Nissant, Antoine, Bloedel, James R., Bracha, Vlastislav, Highstein, Stephen M., Scudder, Charles A., Kachur, Torah M., Pilgrim, Dave B., André, Holley, Mindell, Joseph A., Maduke, Merritt, Ormond, John, Woodin, Melanie A., Datta, Subimal, Eisenstat, David D., Severinsen, Kaare, Jakobsen, Johannes, Merrow, Martha, Roenneberg, Till, Schall, Jeffrey D., Vogt, Brent A., Morecraft, Robert J., Tischkau, Shelley, Gerkema, Menno P., Buijs, Ruud M., Lewy, Alfred J., Hazlerigg, David, Yamamoto, Takashi, Epstein, Marcelo, Ripperger, Jürgen A., Albrecht, Urs, Kramer, Achim, Ruggero, Mario A., Shannon, Robert V., Malmierca, Manuel S., Smith, Philip H., Sodian, Beate, Nieder, Andreas, Mast, Fred W., Godde, Ben, Hansen, Thorsten, Gegenfurtner, Karl R., Faure, Philippe, Allan, Douglas W., Asoh, Hideki, Jänig, Wilfrid, Rybak, Ilya A., Smith, Jeffrey C., Karniel, Amir, Sanguineti, Vittorio, Mansergh, Fiona, R.Wolpaw, Jonathan, McFarland, Dennis J., Mareschal, Denis, Althaus, Nadja, Lee, Tai Sing, Cleland, Thomas A., Goodwin, Graham C., Feuer, Arie, Latash, Mark L., Marín, Oscar, Lucassen, Paul J., Boekhoorn, Karin, Francis, Fiona, Groenewegen, Henk J., Ogawa, Hisashi, Macefield, Vaughan G, Birznieks, Ingvars, Biel, Martin, Binder, Marc D., editor, Hirokawa, Nobutaka, editor, and Windhorst, Uwe, editor

Published
2009
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8. Bacterial sensing via neuronal Nod2 regulates appetite and body temperature

Author

Ilana Gabanyi, Gabriel Lepousez, Richard Wheeler, Alba Vieites-Prado, Antoine Nissant, Sébastien Wagner, Carine Moigneu, Sophie Dulauroy, Samia Hicham, Bernadette Polomack, Florine Verny, Philip Rosenstiel, Nicolas Renier, Ivo Gomperts Boneca, Gérard Eberl, Pierre-Marie Lledo, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Toxines bactériennes - Bacterial Toxins, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Christian-Albrechts University of Kiel, Institutional support was provided by Institut Pasteur, CNRS, and Inserm. Also supported by Pasteur-Roux postdoctoral fellowships from the Institut Pasteur (I.G.), a Human Frontier Science Program fellowship (I.G.), Agence Nationale de la Recherche grant ANR-16-CE15-0021 (I.G.B., P.-M.L., G.C. and G.E.), DFG CRC1182 project C2 (P.R.), and life insurance company 'AG2R-La-Mondiale' (P.-M.L.)., We thank S. Saha, E. de Launoit, and T. Topilko for their help in conducting and/or analyzing experiments, G. Chevalier for his preliminary work on Nod2GFP mice, and D. Mucida and G. M. Silva for their insightful discussions and critical reading and editing of the manuscript. We would also like to thank P. Campagne from the Hub of Bioinformatics and Biostatistics of the Institut Pasteur for his advice on the statistical tests used in this work and the members of the Animalerie Centrale of the Institut Pasteur for maintenance and care of the mice used in this work. We also thank the members of the Microenvironment & Immunity Unit, the laboratory for Perception & Memory, the Stroma, Inflammation & Tissue Repair Unit, and the Biology and Genetics of the Bacterial Cell Wall Unit, for their support and feedback., ANR-16-CE15-0021,PG-Brain,Modulation de l'activité du cerveau par le peptidoglycan bactérien(2016), lepousez, gabriel, Modulation de l'activité du cerveau par le peptidoglycan bactérien - - PG-Brain2016 - ANR-16-CE15-0021 - AAPG2016 - VALID, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Neurons, Mice, Multidisciplinary, Bacteria, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Nod2 Signaling Adaptor Protein, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Animals, Appetite, Peptidoglycan, digestive system diseases, Body Temperature
Abstract

International audience; Gut bacteria influence brain functions and metabolism. We investigated whether this influence can be mediated by direct sensing of bacterial cell wall components by brain neurons. In mice, we found that bacterial peptidoglycan plays a major role in mediating gut-brain communication via the Nod2 receptor. Peptidoglycan-derived muropeptides reach the brain and alter the activity of a subset of brain neurons that express Nod2. Activation of Nod2 in hypothalamic inhibitory neurons is essential for proper appetite and body temperature control, primarily in females. This study identifies a microbe-sensing mechanism that regulates feeding behavior and host metabolism.

Published
2022
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9. Bacterial sensing via neuronal Nod2 regulates appetite and body temperature

Author

Gabanyi, Ilana, primary, Lepousez, Gabriel, additional, Wheeler, Richard, additional, Vieites-Prado, Alba, additional, Nissant, Antoine, additional, Wagner, Sébastien, additional, Moigneu, Carine, additional, Dulauroy, Sophie, additional, Hicham, Samia, additional, Polomack, Bernadette, additional, Verny, Florine, additional, Rosenstiel, Philip, additional, Renier, Nicolas, additional, Boneca, Ivo Gomperts, additional, Eberl, Gérard, additional, and Lledo, Pierre-Marie, additional

Published
2022
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10. Long-range GABAergic projections contribute to cortical feedback control of sensory processing

Author

Pierre-Marie Lledo, Soham Saha, Antoine Nissant, Enzo Peroni, Camille Mazo, Gabriel Lepousez, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was supported by the life insurance company 'AG2R-La-Mondiale', the Agence Nationale de la Recherche (ANR-15-CE37-0004 'SmellBrain' and ANR-16-CE37-0010 'ORUPS') and the Laboratoire d’Excellence Revive (Investissement d’Avenir, ANR-10-LABX-73). Our laboratory is part of the Ecole des Neurosciences de Paris (ENP) Ile-de-France network and is affiliated with the Bio-Psy Laboratory of Excellence. C.M. is a recipient of a fellowship from the French Ministère de l’Education Supérieure et de la Recherche and was also supported by the Fondation de la Recherche Médicale (FDT20160435483). S.S. acknowledges funding from the ENP Graduate program and the Labex Revive consortium for his doctoral program. C.M. and S.S acknowledge the ED3C doctoral school of the Sorbonne Université., We thank Sara Moberg for comments on the manuscript. We also thank Carine Moigneu for viral injections, Julien Grimaud and Lucie Dixsaut for early works. We also wish to thank Uwe Maskos and David DiGregorio from the Institut Pasteur for the gift of SST-Cre, PV-Cre and VIP-Cre mice. We also thank the Genetically-Encoded Neuronal Indicator and Effector (GENIE) Project and the Janelia Farm Research Campus of the Howard Hughes Medical Institute for sharing GCaMP6f constructs, ANR-15-CE37-0004,SmellBrain,Dissection fonctionnelle des circuits codant pour la récompense dans le système olfactif(2015), ANR-16-CE37-0010,ORUPS,Représentation sensorielle lors d'états psychotiques(2016), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Olfactory system, [SDV]Life Sciences [q-bio], Population, General Physics and Astronomy, Sensory system, Optogenetics, Biology, Inhibitory postsynaptic potential, Somatosensory system, General Biochemistry, Genetics and Molecular Biology, Feedback, Centrifugal, GABAergic Neurons, education, education.field_of_study, Multidisciplinary, [SCCO.NEUR]Cognitive science/Neuroscience, Sensory circuits, Olfactory Pathways, General Chemistry, Top-down, Olfactory Bulb, Inhibitory, Olfactory bulb, Smell, Odorants, GABAergic, Perception, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Barrel cortex, Neuroscience
Abstract

In sensory systems, cortical areas send excitatory projections back to subcortical areas to dynamically adjust sensory processing. Here, we uncover for the first time the existence of a cortical inhibitory feedback to subcortical sensory areas. Investigating the olfactory system, we reveal that a subpopulation of GABAergic neurons in the anterior olfactory cortex target the olfactory bulb. Analogous inhibitory cortico-thalamic projections were also present in the somatosensory system. Long-range inhibitory inputs synapsed with both local and output neurons of the olfactory bulb. At the functional level, optogenetic activation of cortical GABAergic projections caused a net subtractive inhibition of both spontaneous and odor-evoked activity in local as well as output projection neurons, mitral and tufted cells. In tufted cells, but not mitral cells, this resulted in an enhanced separation of population odor responses. Furthermore, GABAergic corticofugal projections entrained network oscillations in the communication band between the cortex and the olfactory bulb. Targeted pharmacogenetic silencing of the cortical GABAergic outputs in the olfactory bulb impaired discrimination of similar odor mixtures. Thus, cortical GABAergic feedback represents a new circuit motif in sensory systems involved in refining sensory processing and perception.

Published
2020
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11. GABAergic inhibition at dendrodendritic synapses tunes [gamma] oscillations in the olfactory bulb

Author

Lagier, Samuel, Panzanelli, Patrizia, Russo, Raul E., Nissant Antoine, Bathellier, Brice, Sassoe-Pognetto, Marco, Fritschy, Jean-Marc, and Lledo, Pierre-Marie

Subjects
Olfactory receptors -- Research, GABA -- Receptors, GABA -- Research, Science and technology
Abstract

In the olfactory bulb (OB), odorants induce oscillations in the [gamma], range (20-80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic inhibition back onto mitral cells. Although this reciprocal synapse is thought to be a key element supporting oscillatory activity, the mechanisms by which dendrodendritic inhibition induces and maintains [gamma] oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the [GABA.sub.A] receptor [alpha]1-subunit, which is specifically expressed in mitral cells but not in granule cells. The spontaneous inhibitory postsynaptic current frequency in these mutants was low and was consistent with the reduction of [GABA.sub.A] receptor clusters detected by immunohistochemistry. The remaining [GABA.sub.A] receptors in mitral cells contained the [alpha]3-subunit and supported slower decaying currents of unchanged amplitude. Overall, inhibitory-mediated interactions between mitral cells were smaller and slower in mutant than in WT mice, although the strength of sensory afferent inputs remained unchanged. Consequently, both experimental and theoretical approaches revealed slower [gamma] oscillations in the OB network of mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are strongly constrained by the precise location, subunit composition and kinetics of [GABA.sub.A] receptors expressed in mitral cells. [alpha]1 knockout | [GABA.sub.A] receptor | olfaction | reciprocal synapses

Published
2007

12. Similar chloride channels in the connecting tubule and cortical collecting duct of the mouse kidney

Author

Nissant, Antoine, Paulais, Marc, Lachheb, Sahran, Lourdel, Stephane, and Teulon, Jacques

Subjects
Clathrate compounds -- Research, Kidney tubules -- Research, Kidney tubules -- Analysis, Biological sciences
Abstract

Using the patch-clamp technique, we investigated [Cl.sup.-] channels on the basolateral membrane of the connecting tubule (CNT) and cortical collecting duct (CCD). We found a ~10-pS channel in CNT cell-attached patches. Substitution of sodium gluconate for NaCl in the pipette shifted the reversal potential by +25 mV, whereas N-methyl-Dg-luconate chloride had no effect, indicating anion selectivity. On inside-out patches, we determined a selectivity sequence of [Cl.sup.-] > [Br.sup-] ~ N[Osup.-.sub.3] > [F.sup.-], which is compatible with that of CIC-K2, a [Cl.sup.-] channel in the distal nephron. In addition, the number of open channels (N[P.sub.o]) measured in cell-attached patches was significantly increased when [Ca.sup.2+] concentration or pH in the pipette was increased, which is another characteristic of CIC-K. These findings suggest that the basis for this channel is CIC-K2. A similar [Cl.sup.-] channel was found in CCD patches. Because CNT and CCD are heterogeneous tissues, we studied the cellular distribution of the [Cl.sup.-] channel using recording conditions (KCl-rich solution in the pipette) that allowed us to detect simultaneously [Cl.sup.-] channels and inwardly rectifying [K.sup.+] channels. We detected [Cl.sup.-] channels alone in 45% and 42% and [K.sup.+] channels alone in 51% and 58% of CNT and CCD patches, respectively. [Cl.sup.-] and [K.sup.+] channels were recorded simultaneously from two patches (4% of patches) in the CNT and from none of the patches in the CCD. This indicates that [Cl.sup.-] and [K.sup.+] channels are located in different cell types, which we suggest may be the intercalated cells and principal cells, respectively. ClC-K; renal tubule; intercalated cell

Published
2006

13. Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp

Author

Nissant, Antoine, Lourdel, Stephane, Baillet, Sophie, Paulais, Marc, Marvao, Pedro, Teulon, Jacques, and Imbert-Teboul, Martine

Subjects
Chloride channels -- Research, Biological sciences
Abstract

The distal convoluted tubule (DCT) is a heterogeneous segment subdivided into early (DCT1) and late (DCT2) parts, depending on the distribution of various transport systems. We do not have an exhaustive picture of the [C1.sup.-] channels on the basolateral side: the presence of C1C-K2 channels is generally accepted, whereas that of C1C-K1 remains controversial. We used here single-cell RT-PCR and patch clamp to probe [C1.sup.-] channel heterogeneity in microdissected mouse DCT at the molecular and functional levels. Our findings show that 63% of the DCT cells express C1C-K2 mRNA, either alone (type 1 cells: 47 and 23% in DCT1 and DCT2, respectively), or combined with C1C-K1, mostly in DCT2 (type 2 cells: 33%), but 37% of DCT1 and DCT2 cells do not express any C1C-K. Patch-clamp experiments revealed that a [C1.sup.-] channel, with 9-pS conductance and [C1.sup.-] > N[O.sub.3] = [Br.sup.-] anion selectivity sequence, is present in the DCT1 and DCT2 basolateral membranes (87 and 71% of the patches, respectively). This dominant channel is likely to be C1C-K2 in type 1 cells. In type 2 cells, it could be C1C-K2 and/or C1C-K1 homodimers, but also C1C-K1/C1C-K2 heterodimers, or a mixture of all combinations. A second, distinct [C1.sup.-] channel (13% of DCT1 patches, 29% of DCT2 patches) also displayed 9-pS conductance but had a completely different anion selectivity ([I.sup.-] > N[O.sup.-.sub.3] > Br > [Cl.sup.-]), which was not compatible with that of the C1C-Ks. This indicates that a [Cl.sup.-] channel that is unlikely to belong to the C1C family may also be involved in [C1.sup.-] absorption in the DCT2. kidney; C1C-K; sodium chloride absorption

Published
2004

14. A chloride channel at the basolateral membrane of the distal-convoluted tubule: a candidate ClC-K channel

Author

Lourdel, Stephane, Paulais, Marc, Marvao, Pedro, Nissant, Antoine, and Teulon, Jacques

Subjects
Chloride channels -- Physiological aspects, Kidneys -- Physiological aspects, Biological sciences, Health
Abstract

The distal-convoluted tubule (DCT) of the kidney absorbs NaCl mainly via an [Na.sup.+]-[Cl.sup.-] cotransporter located at the apical membrane, and [Na.sup.+], [K.sup.+] ATPase at the basolateral side. [Cl.sup.-] transport across the basolateral membrane is thought to be conductive, but the corresponding channels have not yet been characterized. In the present study, we investigated [Cl.sup.-] channels on microdissected mouse DCTs using the patch-clamp technique. A channel of ~9 pS was found in 50% of cell-attached patches showing anionic selectivity. The N[P.sub.0] in cell-attached patches was not modified when tubules were preincubated in the presence of [10.sup.-5] M forskolin, but the channel was inhibited by phorbol ester ([10.sup.-6] M). In addition, N[P.sub.0] was significantly elevated when the calcium in the pipette was increased from 0 to 5 mM (N[P.sub.0] increased threefold), or pH increased from 6.4 to 8.0 (N[P.sub.0] increased 15-fold). Selectivity experiments conducted on inside-out patches showed that the [Na.sup.+] to [Cl.sup.-] relative permeability was 0.09, and the anion selectivity sequence [Cl.sup.-] ~ [I.sup.-] > [Br.sup.-] ~ N[O.sub.3.sup.-] > [F.sup.-]. Intracellular NPPB ([10.sup.-4] M) and DPC ([10.sup.-3] M) blocked the channel by 65% and 80%, respectively. The channel was inhibited at acid intracellular pH, but intracellular ATP and PKA had no effect. ClC-K [Cl.sup.-] channels are characterized by their sensitivity to the external calcium and to pH. Since immunohistochemical data indicates that ClC-K2, and perhaps ClC-K1, are present on the DCT basolateral membrane, we suggest that the channel detected in this study may belong to this subfamily of the ClC channel family. KEY WORDS: chloride channel * ClC-K * kidney * PKC * patch-clamp

Published
2003

18. The endocannabinoid system controls food intake via olfactory processes

Author

Hans-Christian Pape, Theresa Wiesner, Hirac Gurden, Anna Chiarlone, Aya Wadleigh, Pierre-Marie Lledo, Luigi Bellocchio, Guillaume Ferreira, Federico Massa, Danièle Verrier, Claire Martin, Manuel Guzmán, Peggy Vincent, Tiffany Desprez, Gabriel Lepousez, Astrid Cannich, Leire Reguero, Beat Lutz, Pedro Grandes, Sabine Ruehle, Antoine Nissant, Giovanni Marsicano, Mounir Bendahmane, Floor Remmers, Edgar Soria-Gomez, Isabelle Matias, Carmelo Quarta, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), University of Bologna/Università di Bologna, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, This work was supported by INSERM (G.M.), EU-Fp7 (REPROBESITY, HEALTH-F2-2008-223713, G.M.), European Research Council (ENDOFOOD, ERC-2010-StG-260515, G.M.), Fondation pour la Recherche Medicale (FRM-DRM-20101220445, G.M.), Region Aquitaine (G.M.), LABEX BRAIN (ANR-10-LABX-43), Fyssen Foundation (E.S.-G.), EMBO Post-doc Fellowship (L.B.), RTA, I.S. Carlos III (RD12/0028/0004, P.G.), Basque Country Government BCG IT764-13 (P.G.), University of the Basque Country UFI11/41 (P.G.), MINECO BFU2012-33334 (P.G.), Postdoctoral Specialization Contract from the University of the Basque Country UPV/EHU (L.R.), MINECO SAF2012-35759 (M.G.), Deutsche Forschungsgemeinschaft (SFB-TRR 58, B.L. and H.-C.P.), CONACyT (E.S.-G.). The Lledo laboratory is part of the École des Neurosciences de Paris Ile-de-France network, a member of the Bio-Psy Labex and is supported partially by 'AG2R-La-Mondiale'., We thank D. Gonzales, N. Aubailly and all of the personnel of the Animal Facility of the NeuroCentre Magendie for mouse care and genotyping, A. Desprez for help with the odor task set-up, D. Herrera and S. Rahayel (NutriBrain School 2012) for help with some experiments, all of the members of the Marsicano laboratory for useful discussions, A. Bacci, D. Cota, V. Deroche and M. Valley for critically reading the manuscript, and K. Deisseroth (Stanford University) and B.L. Roth (University of North Carolina) for providing the plasmids coding for ChR2 and DREADD, respectively., ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), European Project: 223713,EC:FP7:HEALTH,FP7-HEALTH-2007-B,REPROBESITY(2008), European Project: 260515,EC:FP7:ERC,ERC-2010-StG_20091118,ENDOFOOD(2011), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Complutense University of Madrid (UCM), University of the Basque Country [Bizkaia] (UPV/EHU), Perception et Mémoire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Johannes Gutenberg - University of Mainz (JGU), Westfälische Wilhelms-Universität Münster (WWU), University of Bologna, Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, ANR-10-IDEX-03-02/10-LABX-0043,BRAIN,Bordeaux Region Aquitaine Initiative for Neuroscience(2010), ANR-11-IDEX-0004-02/11-LABX-0035,BIOPSY,Laboratoire de Psychiatrie Biologique(2011), Johannes Gutenberg - Universität Mainz (JGU), and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique

Subjects
Male, Olfactory system, MESH: Olfactory Perception, Cannabinoid receptor, MESH: Feedback, Physiological, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MESH: Cannabinoid Receptor Agonists, MESH: Endocannabinoids, MESH: Receptor, Cannabinoid, CB1, Synaptic Transmission, MESH: Mice, Knockout, MESH: Eating, Eating, Mice, Olfactory bulb, Receptor, Cannabinoid, CB1, MESH: Animals, Feedback, Physiological, Mice, Knockout, musculoskeletal, neural, and ocular physiology, General Neuroscience, digestive, oral, and skin physiology, Olfactory Pathways, Endocannabinoid system, MESH: Feeding Behavior, lipids (amino acids, peptides, and proteins), psychological phenomena and processes, MESH: Olfactory Bulb, Biology, Inhibitory postsynaptic potential, Glutamatergic, MESH: Mice, Inbred C57BL, MESH: Synaptic Transmission, medicine, Animals, MESH: Mice, Cannabinoid Receptor Agonists, Feeding Behavior, Olfactory Perception, MESH: Male, Mice, Inbred C57BL, nervous system, Odor, Feeding behaviour, Cannabinoid, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Neuroscience, MESH: Olfactory Pathways, Endocannabinoids
Abstract

Comment in Sensory systems: the hungry sense. [Nat Rev Neurosci. 2014] Inhaling: endocannabinoids and food intake. [Nat Neurosci. 2014]; International audience; Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit. Our data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.

Published
2014
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19. Renal Chloride Channels in Relation to Sodium Chloride Transport

Author

Planelles, Gabrielle, Sepúlveda, Francisco, Andrini, Olga, Terjung, Ronald, Pinelli, Laurent, Nissant, Antoine, Edwards, Aurélie, Lourdel, Stéphane, Teulon, Jacques, Paulais, Marc, Canalopathies épithéliales: la mucoviscidose et autres maladies, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centro de Estudios Científicos (CECs), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemical and Biological Engineering, Tufts University [Medford], Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
urogenital system, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience; ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells.

Published
2016
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20. Double régulation par le voltage et le pH du canal chlorure ClC-K2 du néphron distal

Author

Pinelli, Laurent, Nissant, Antoine, Edwards, Aurélie, Lourdel, Stéphane, Teulon, Jacques, Paulais, Marc, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemical and Biological Engineering, Tufts University [Medford], Génomique, physiologie et physiopathologie rénales, Université Pierre et Marie Curie - Paris 6 (UPMC)-UMRS 872, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016
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21. Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH

Author

Aurélie Edwards, Marc Paulais, Laurent Pinelli, Jacques Teulon, Stéphane Lourdel, Antoine Nissant, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), and HAL-UPMC, Gestionnaire

Subjects
[ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0301 basic medicine, Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physiology, Intracellular pH, Anion Transport Proteins, Gating, Sodium Chloride, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, Mice, 0302 clinical medicine, Chlorides, Chloride Channels, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, Intercalated Cell, Research Articles, Epithelial polarity, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Chemistry, urogenital system, Cell Membrane, Depolarization, Nephrons, Hydrogen-Ion Concentration, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Connecting tubule, 030104 developmental biology, medicine.anatomical_structure, Biochemistry, Chloride channel, Biophysics, Calcium, Ion Channel Gating, 030217 neurology & neurosurgery, Intracellular, Research Article
Abstract

ClC-K2 is present on the basolateral membrane of kidney epithelial cells, but little is known about its single channel properties. Pinelli et al. record unitary ClC-K2 currents from intercalated cells of mouse connecting tubules and investigate their regulation by voltage, pH, Cl−, and Ca2+., ClC-K2, a member of the ClC family of Cl− channels and transporters, forms the major basolateral Cl− conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl− absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl−, and Ca2+ on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca2+ strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl− has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl−/HCO3− exchange in type B intercalated cells.

Published
2016
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22. Abnormal Neuronal Migration Changes the Fate of Developing Neurons in the Postnatal Olfactory Bulb

Author

Antoine Nissant, Pierre-Marie Lledo, and Richard Belvindrah

Subjects
Doublecortin Domain Proteins, Doublecortin Protein, Rostral migratory stream, Neurogenesis, Subventricular zone, Biology, Mice, Cell Movement, medicine, Animals, Neurons, General Neuroscience, Electroporation, Neuropeptides, Articles, Olfactory Bulb, Olfactory bulb, Doublecortin, Mice, Inbred C57BL, medicine.anatomical_structure, Animals, Newborn, nervous system, Forebrain, biology.protein, GABAergic, Calretinin, Microtubule-Associated Proteins, Neuroscience
Abstract

Neuronal precursors are continuously integrated into the adult olfactory bulb (OB). The vast majority of these precursor cells originates from the subventricular zone and migrates along the rostral migratory stream (RMS) en route to the OB. This process, called postnatal neurogenesis, results from intricate pathways depending both on cell-autonomous factors and extrinsic regulation provided by the local environment. Using electroporation in postnatal mice to label neuronal precursors with green fluorescent protein (GFP) and to reduce the expression levels of doublecortin (DCX) with short-hairpin (Sh) RNA, we investigated the consequences of impairing migration on the fate of postnatal-formed neurons. First, we showed that electroporation of Dcx ShRNA plasmid efficiently knocks down the expression of DCX and disrupts cells migration along the RMS. Second, we found misplaced anomalous migrating cells that displayed defects in polarity and directionality. Third, patch-clamp recordings performed at 5–7 days post-electroporation (dpe) revealed increased density of voltage-dependent Na+channels and enhanced responsiveness to GABAAreceptor agonist. At later time points (i.e., 12 and 30 dpe), most of the Dcx ShRNA+cells developed in the core of the OB and displayed aberrant dendritic length and branching. Additional analysis revealed the formation of GABAergic and glutamatergic synaptic inputs on the mispositioned neurons. Finally, quantifying fate determination by numbering the proportion of GFP+/calretinin+newborn neurons revealed that Dcx ShRNA+cells acquire mature phenotype despite their immature location. We conclude that altering the pace of migration at early stages of postnatal neurogenesis profoundly modifies the tightly orchestrated steps of neuronal maturation, and unveils the influence of microenvironment on controlling neuronal development in the postnatal forebrain.

Published
2011
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23. Integration and maturation of newborn neurons in the adult olfactory bulb - from synapses to function

Author

Marta Pallotto and Antoine Nissant

Subjects
nervous system, Functional integration (neurobiology), General Neuroscience, Neurogenesis, Neuroplasticity, Synaptogenesis, Olfactory memory, Biology, Cell Maturation, Neuroscience, Function (biology), Olfactory bulb
Abstract

In adult mammals, thousands of new neurons integrate in the olfactory bulb (OB) each day. This process of adult neurogenesis has received a great deal of scientific attention aimed at understanding how mature neural networks withstand neuronal replacement, and medical interest to explore the promise that these cells may be manipulated for brain repair therapies. In the present review, we focus on the mechanisms and consequences of the functional integration of newborn interneurons in the OB network. We first describe the steps of synaptic integration and functional maturation of adult-born interneurons in the OB. We then examine the physiological control of cell maturation and survival. Finally, we explore the potential impact of adult neurogenesis on the function of the OB.

Published
2011
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24. GABAergic inhibition at dendrodendritic synapses tunes γ oscillations in the olfactory bulb

Author

Samuel Lagier, Brice Bathellier, Pierre-Marie Lledo, Marco Sassoè-Pognetto, Jean-Marc Fritschy, Patrizia Panzanelli, Raúl E. Russo, Antoine Nissant, Perception et Mémoire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Pharmacology and Forensic Medicine, Università degli studi di Torino = University of Turin (UNITO), Neurofisiolgía Celulary Molecular, Instituto de Investigaciones Biológicas, Laboratory of Computational Neuroscience [Lausanne] (LCN-EPFL), Ecole Polytechnique Fédérale de Lausanne (EPFL)-Brain and Mind Institute, Istituto Nazionale di Neuroscienze, Institute of Pharmacology and Toxicology [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Università degli studi di Torino (UNITO)

Subjects
MESH: Olfactory Bulb, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Models, Neurological, MESH: gamma-Aminobutyric Acid, Biology, Neurotransmission, MESH: Dendrites, MESH: Phenotype, Inhibitory postsynaptic potential, gamma-Aminobutyric acid, MESH: Synapses, GABAA-rho receptor, Synapse, Mice, 03 medical and health sciences, 0302 clinical medicine, MESH: Models, Neurological, medicine, Animals, MESH: Animals, α1 knockout GABAA receptor olfaction reciprocal synapses, Receptor, MESH: Mice, MESH: Receptors, GABA-A, MESH: Inhibitory Postsynaptic Potentials, gamma-Aminobutyric Acid, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Glutamate receptor, Dendrites, Anatomy, Biological Sciences, Receptors, GABA-A, Olfactory Bulb, Olfactory bulb, Phenotype, Inhibitory Postsynaptic Potentials, Synapses, Biophysics, 030217 neurology & neurosurgery, medicine.drug
Abstract

In the olfactory bulb (OB), odorants induce oscillations in the γ range (20–80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic inhibition back onto mitral cells. Although this reciprocal synapse is thought to be a key element supporting oscillatory activity, the mechanisms by which dendrodendritic inhibition induces and maintains γ oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the GABA A receptor α1-subunit, which is specifically expressed in mitral cells but not in granule cells. The spontaneous inhibitory postsynaptic current frequency in these mutants was low and was consistent with the reduction of GABA A receptor clusters detected by immunohistochemistry. The remaining GABA A receptors in mitral cells contained the α3-subunit and supported slower decaying currents of unchanged amplitude. Overall, inhibitory-mediated interactions between mitral cells were smaller and slower in mutant than in WT mice, although the strength of sensory afferent inputs remained unchanged. Consequently, both experimental and theoretical approaches revealed slower γ oscillations in the OB network of mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are strongly constrained by the precise location, subunit composition and kinetics of GABA A receptors expressed in mitral cells.

Published
2007
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25. GABAB Receptors Tune Cortical Feedback to the Olfactory Bulb

Author

Pierre-Marie Lledo, Antoine Nissant, Camille Mazo, Gabriel Lepousez, Matthew T. Valley, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Olfactory system, Light, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Channelrhodopsin, Action Potentials, Sensory system, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Mice, Transgenic, Olfaction, Optogenetics, Biology, In Vitro Techniques, Inhibitory postsynaptic potential, Feedback, 03 medical and health sciences, Mice, 0302 clinical medicine, Calcium imaging, Channelrhodopsins, synapse, Quinoxalines, Excitatory Amino Acid Agonists, Animals, sensory circuits, Anesthetics, Local, General Neuroscience, Excitatory Postsynaptic Potentials, Lidocaine, Olfactory Pathways, Articles, Olfactory Bulb, Olfactory bulb, Mice, Inbred C57BL, Smell, 030104 developmental biology, Olfactory Cortex, nervous system, Receptors, GABA-B, top-down, oscillations, Odorants, feedforward inhibition, Neuroscience, 030217 neurology & neurosurgery, olfaction
Abstract

Sensory perception emerges from the confluence of sensory inputs that encode the composition of external environment and top-down feedback that conveys information from higher brain centers. In olfaction, sensory input activity is initially processed in the olfactory bulb (OB), serving as the first central relay before being transferred to the olfactory cortex. In addition, the OB receives dense connectivity from feedback projections, so the OB has the capacity to implement a wide array of sensory neuronal computation. However, little is known about the impact and the regulation of this cortical feedback. Here, we describe a novel mechanism to gate glutamatergic feedback selectively from the anterior olfactory cortex (AOC) to the OB. Combining in vitro and in vivo electrophysiological recordings, optogenetics, and fiber-photometry-based calcium imaging applied to wild-type and conditional transgenic mice, we explore the functional consequences of circuit-specific GABA type-B receptor (GABA(B)R) manipulation. We found that activation of presynaptic GABA(B)Rs specifically depresses synaptic transmission from the AOC to OB inhibitory interneurons, but spares direct excitation to principal neurons. As a consequence, feedforward inhibition of spontaneous and odor-evoked activity of principal neurons is diminished. We also show that tunable cortico-bulbar feedback is critical for generating beta, but not gamma, OB oscillations. Together, these results show that GABA(B)Rs on cortico-bulbar afferents gate excitatory transmission in a target-specific manner and thus shape how the OB integrates sensory inputs and top-down information. SIGNIFICANCE STATEMENT The olfactory bulb (OB) receives top-down inputs from the olfactory cortex that produce direct excitation and feedforward inhibition onto mitral and tufted cells, the principal neurons. The functional role of this feedback and the mechanisms regulating the balance of feedback excitation and inhibition remain unknown. We found that GABA(B) receptors are expressed in cortico-bulbar axons that synapse on granule cells and receptor activation reduces the feedforward inhibition of spontaneous and odor-driven mitral and tufted cells' firing activity. In contrast, direct excitatory inputs to these principal neurons remain unchanged. This study demonstrates that activation of GABA(B) receptors biases the excitation/inhibition balance provided by cortical inputs to the OB, leading to profound effects on early stages of sensory information processing.

Published
2015
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26. Adult neurogenesis and the future of the rejuvenating brain circuits

Author

Antoine Nissant, Gabriel Lepousez, Pierre-Marie Lledo, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the life insurance company Humanis and the Agence Nationale de la Recherche (ANR-BLAN-SVSE4-LS-110624 and PLASTMATBEHAV). Our laboratory is also part of the École des Neurosciences de Paris (ENP) Ile-de-France network, and it is supported by French state funds managed by the ANR within the Investissements d’Avenir programme 'Biopsy' and 'Revive.', ANR-12-BSV7-0017,PLASTMATBEHAV,Contribution de la neurogenèse olfactive à la mise en place du comportement maternel chez les mammifères.(2012), ANR-15-CE37-0004,SmellBrain,Dissection fonctionnelle des circuits codant pour la récompense dans le système olfactif(2015), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, MESH: Forecasting, Biomedical Research, MESH: Hippocampus, Neurogenesis, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, MESH: Neurons, MESH: Mental Recall, MESH: Rejuvenation, Biology, Regenerative Medicine, Hippocampus, medicine, Humans, Rejuvenation, MESH: Neuronal Plasticity, Neurons, Systems neuroscience, Adaptive behavior, Brain Diseases, Neuronal Plasticity, MESH: Humans, General Neuroscience, Regeneration (biology), MESH: Biomedical Research, [SCCO.NEUR]Cognitive science/Neuroscience, MESH: Adult, Human brain, Mammalian brain, MESH: Neurogenesis, Chromosome Pairing, medicine.anatomical_structure, MESH: Chromosome Pairing, MESH: Nerve Net, MESH: Regenerative Medicine, Mental Recall, Nerve Net, Neuroscience, Forecasting
Abstract

International audience; For a long time, the mammalian brain has been perceived to be a static organ. However, the discovery of adult neurogenesis in most mammalian species, including humans, monkeys, and rodents, has disrupted this view. As this continuous regeneration has an effect on established behavioral patterns, it holds promising therapeutic potential. However, before harnessing this potential regenerative power, we must understand what effects new neurons have on existing brain circuits. Ongoing research contributes to several important steps toward bridging the gap between adult-born neurons, circuits, and behavior. The study of adult neurogenesis in different neurogenic regions from a systems neuroscience perspective will pave the way to understanding how it supports adaptive behavior and why its dysfunction correlates with some human brain disorders.

Published
2015
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27. Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp

Author

Jacques Teulon, Antoine Nissant, Marc Paulais, Sophie Baillet, Stéphane Lourdel, Pedro Marvao, Martine Imbert-Teboul, Laboratoire de physiologie et génomique rénales (CNRS UMR7134 - Institut des Cordeliers), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Cordeliers [Paris], and Paulais, Marc

Subjects
Bromides, Male, Patch-Clamp Techniques, Physiology, Cell, 030232 urology & nephrology, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Gene Expression, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Absorption, Mice, 03 medical and health sciences, 0302 clinical medicine, Chlorides, Chloride Channels, medicine, Animals, Distribution (pharmacology), RNA, Messenger, Distal convoluted tubule, Patch clamp, Kidney Tubules, Distal, 030304 developmental biology, 0303 health sciences, Nitrates, Reverse Transcriptase Polymerase Chain Reaction, urogenital system, Chemistry, Electric Conductivity, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Anatomy, Hydrogen-Ion Concentration, Iodides, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, medicine.anatomical_structure, Real-time polymerase chain reaction, Biophysics, Chloride channel
Abstract

The distal convoluted tubule (DCT) is a heterogeneous segment subdivided into early (DCT1) and late (DCT2) parts, depending on the distribution of various transport systems. We do not have an exhaustive picture of the Cl−channels on the basolateral side: the presence of ClC-K2 channels is generally accepted, whereas that of ClC-K1 remains controversial. We used here single-cell RT-PCR and patch clamp to probe Cl−channel heterogeneity in microdissected mouse DCT at the molecular and functional levels. Our findings show that 63% of the DCT cells express ClC-K2 mRNA, either alone (type 1 cells: 47 and 23% in DCT1 and DCT2, respectively), or combined with ClC-K1, mostly in DCT2 (type 2 cells: 33%), but 37% of DCT1 and DCT2 cells do not express any ClC-K. Patch-clamp experiments revealed that a Cl−channel, with 9-pS conductance and Cl−> NO3−= Br−anion selectivity sequence, is present in the DCT1 and DCT2 basolateral membranes (87 and 71% of the patches, respectively). This dominant channel is likely to be ClC-K2 in type 1 cells. In type 2 cells, it could be ClC-K2 and/or ClC-K1 homodimers, but also ClC-K1/ClC-K2 heterodimers, or a mixture of all combinations. A second, distinct Cl−channel (13% of DCT1 patches, 29% of DCT2 patches) also displayed 9-pS conductance but had a completely different anion selectivity (I−> NO3−> Br−> Cl−), which was not compatible with that of the ClC-Ks. This indicates that a Cl−channel that is unlikely to belong to the ClC family may also be involved in Cl−absorption in the DCT2.

Published
2004
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28. Similar chloride channels in the connecting tubule and cortical collecting duct of the mouse kidney

Author

Jacques Teulon, Antoine Nissant, Marc Paulais, Sahran Lachheb, Stéphane Lourdel, Paulais, Marc, Laboratoire de physiologie et génomique rénales (CNRS UMR7134 - Institut des Cordeliers), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Cordeliers [Paris], and A. Nissant and S. Lachheb hold a Ph.D. fellowship from the Ministère de la Recherche, and M. Paulais is an Institut National de la Santé et de la Recherche Médicale researcher.

Subjects
Male, Patch-Clamp Techniques, Potassium Channels, Physiology, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Sodium Chloride, 030204 cardiovascular system & hematology, Gluconates, Mice, 03 medical and health sciences, 0302 clinical medicine, Chloride Channels, Interneurons, medicine, Animals, Intercalated Cell, Kidney Tubules, Collecting, 030304 developmental biology, Epithelial polarity, 0303 health sciences, Renal tubule, Chemistry, urogenital system, Electric Conductivity, Anatomy, Hydrogen-Ion Concentration, Connecting tubule, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Kidney Tubules, medicine.anatomical_structure, Chloride channel, Mouse Kidney, Biophysics, Calcium, Duct (anatomy)
Abstract

Using the patch-clamp technique, we investigated Cl−channels on the basolateral membrane of the connecting tubule (CNT) and cortical collecting duct (CCD). We found a ∼10-pS channel in CNT cell-attached patches. Substitution of sodium gluconate for NaCl in the pipette shifted the reversal potential by +25 mV, whereas N-methyl-d-gluconate chloride had no effect, indicating anion selectivity. On inside-out patches, we determined a selectivity sequence of Cl−> Br−∼ NO3−> F−, which is compatible with that of ClC-K2, a Cl−channel in the distal nephron. In addition, the number of open channels ( NPo) measured in cell-attached patches was significantly increased when Ca2+concentration or pH in the pipette was increased, which is another characteristic of ClC-K. These findings suggest that the basis for this channel is ClC-K2. A similar Cl−channel was found in CCD patches. Because CNT and CCD are heterogeneous tissues, we studied the cellular distribution of the Cl−channel using recording conditions (KCl-rich solution in the pipette) that allowed us to detect simultaneously Cl−channels and inwardly rectifying K+channels. We detected Cl−channels alone in 45% and 42% and K+channels alone in 51% and 58% of CNT and CCD patches, respectively. Cl−and K+channels were recorded simultaneously from two patches (4% of patches) in the CNT and from none of the patches in the CCD. This indicates that Cl−and K+channels are located in different cell types, which we suggest may be the intercalated cells and principal cells, respectively.

Published
2006
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31. Anwenderstudie ORBIS - Umfang, Möglichkeiten und Grenzen der Anwendung im Fachhochschulbereich

Author

Lehner, Dominik and Naganathi, Nissant

Subjects
Bureau van Dijk, 330 - Wirtschaft, Datenbank, Orbis
Abstract

Mit einer Abdeckung von weltweit 120 Mio. Unternehmen und einer Vielzahl von Informationsbereichen hat die Orbis Datenbank einen enormen Umfang. Ob die angebotenen Leistungen überzeugen und den Fachhochschulen effektiv von Nutzen sind, bleibt den Lesern dieser Bachelorarbeit nicht vorenthalten.

Published
2013
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32. Integration and maturation of newborn neurons in the adult olfactory bulb--from synapses to function

Author

Antoine, Nissant and Marta, Pallotto

Subjects
Neurons, Adult Stem Cells, Neurogenesis, Synapses, Animals, Cell Differentiation, Nerve Net, Olfactory Bulb
Abstract

In adult mammals, thousands of new neurons integrate in the olfactory bulb (OB) each day. This process of adult neurogenesis has received a great deal of scientific attention aimed at understanding how mature neural networks withstand neuronal replacement, and medical interest to explore the promise that these cells may be manipulated for brain repair therapies. In the present review, we focus on the mechanisms and consequences of the functional integration of newborn interneurons in the OB network. We first describe the steps of synaptic integration and functional maturation of adult-born interneurons in the OB. We then examine the physiological control of cell maturation and survival. Finally, we explore the potential impact of adult neurogenesis on the function of the OB.

Published
2011

33. Fragile X mental retardation protein regulates new neuron differentiation in the adult olfactory bulb

Author

Antoine Nissant, Marie Néant-Fery, Tatiana Mota, Charles A. Greer, Pierre-Marie Lledo, Ben A. Oostra, Alain Trembleau, Isabelle Caillé, Sophie Scotto-Lomassese, and Clinical Genetics

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, Dendritic spine, Patch-Clamp Techniques, Time Factors, Dendritic Spines, Neurogenesis, Green Fluorescent Proteins, Biology, Article, Synapse, Fragile X Mental Retardation Protein, Mice, Microscopy, Electron, Transmission, medicine, Animals, RNA, Small Interfering, Mice, Knockout, Neurons, Analysis of Variance, General Neuroscience, Excitatory Postsynaptic Potentials, Cell Differentiation, Dendrites, Granule cell, medicine.disease, FMR1, Olfactory Bulb, Olfactory bulb, Fragile X syndrome, Mice, Inbred C57BL, medicine.anatomical_structure, Mutation, Synapses, Neuron differentiation, Neuroscience
Abstract

The fragile X mental retardation protein (FMRP) is an RNA-binding protein essential for multiple aspects of neuronal mRNA metabolism. Its absence leads to the fragile X syndrome, the most prevalent genetic form of mental retardation. The anatomical landmark of the disease, also present in theFmr1knock-out (KO) mice, is the hyperabundance of immature-looking lengthened dendritic spines. We used the well known continuous production of adult-born granule cells (GCs) in the mouse olfactory bulb (OB) to analyze the consequences of Fmrp loss on the differentiation of GCs. Morphological analysis of GCs in theFmr1KO mice showed an increase in spine density without a change in spine length. We developed an RNA interference strategy to cell-autonomously mutateFmr1in a wild-type OB network. Mutated GCs displayed an increase in spine density and spine length. Detailed analysis of the spines through immunohistochemistry, electron microscopy, and electrophysiology surprisingly showed that, despite these abnormalities, spines receive normal glutamatergic synapses, and thus that mutated adult-born neurons are synaptically integrated into the OB circuitry. Time-course analysis of the spine defects showed that Fmrp cell-autonomously downregulates the level and rate of spine production and limits their overgrowth. Finally, we report that Fmrp does not regulate dendritogenesis in standard conditions but is necessary for activity-dependent dendritic remodeling. Overall, our study of Fmrp in the context of adult neurogenesis has enabled us to carry out a precise dissection of the role of Fmrp in neuronal differentiation and underscores its pleiotropic involvement in both spinogenesis and dendritogenesis.

Published
2011

35. Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit

Author

Marta Pallotto, Hiroyuki Katagiri, Marco Sassoè-Pognetto, Pierre-Marie Lledo, Kerren Murray, Antoine Nissant, Perception et Mémoire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), National Institute of Neuroscience [Turin, Italy], Università degli studi di Torino = University of Turin (UNITO), This work was supported by the Fondation pour la Recherche Médicale 'Equipe FRM', the Groupe 'Novalis-Taitbout' and the Ecole des Neurosciences de Paris (ENP), Compagnia di San Paolo and Regione Piemonte (Ricerca Sanitaria Finalizzata 2006 and 2008). HK was supported by the Association Pasteur-Japon fellowship. MP is the recipient of a doctoral fellowship from 'Università Italo-Francese' (Progetto Vinci) and Servier. The laboratory is also supported by the Agence Nationale de la Recherche 'ANR-09-NEUR-004' in the frame of 'ERA-NET NEURON' of FP7 program by the European Commission. Dr. Lledo's visit to the Department of Molecular and Cellular Biology, Harvard University (Murthy's laboratory), was funded by the Philippe Foundation., European Project: 291840,EC:FP7:HEALTH,FP7-ERANET-2011-RTD,ERA-NET NEURON II(2012), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and University of Turin

Subjects
0303 health sciences, Interneuron, Rostral migratory stream, Research, musculoskeletal, neural, and ocular physiology, Olfaction, Biology, Olfactory bulb, Synapse, 03 medical and health sciences, Glutamatergic, 0302 clinical medicine, medicine.anatomical_structure, nervous system, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Glutamatergic synapse, Postsynaptic density, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

Published
2011
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39. C

Author

Justin R. Davis, Andrew C. Giles, Catharine H. Rankin, Jonathan Bell, Hiroshi Kimura, Tadashi Uemura, Yoshi Kidokoro, Mado Lemieux, Paul De Koninck, Emilio Carbone, Adriano Senatore, J. David Spafford, Megan J. Dowie, Natasha L. Grimsey, Michelle Glass, Kevin D. Gillis, Peter Hunter, Brian Budgell, Arijit Roy, Richard J. A. Wilson, Okihide Hikosaka, Michael Esfeld, Jens Harbecke, Takayuki Mitsuhashi, Takao Takahashi, Ryoichiro Kageyama, Ryosuke Ohsawa, Toshiyuki Ohtsuka, Peter M. Lalley, Michael N. Nitabach, Julian F. R. Paton, David M. Waitzman, Eugene Nattie, Aihua Li, Ikuo Tsunoda, Mikako Kobayashi-Warren, Jane E. Libbey, Robert S. Fujinami, Amod P. Kulkarni, Laurie A. Kellaway, Girish J. Kotwal, Katrin E. Morgen, Maria Grazia Ciufolini, Loredana Nicoletti, Randall L. Davis, Markus J. Hofer, Iain L. Campbell, Troels S. Jensen, Nanna B. Finnerup, Volko A. Straub, Eduardo E. Benarroch, Adolfo M. Bronstein, Antoine Nissant, James R. Bloedel, Vlastislav Bracha, Stephen M. Highstein, Charles A. Scudder, Torah M. Kachur, Dave B. Pilgrim, Holley André, Joseph A. Mindell, Merritt Maduke, John Ormond, Melanie A. Woodin, Subimal Datta, David D. Eisenstat, Kaare Severinsen, Johannes Jakobsen, Martha Merrow, Till Roenneberg, Jeffrey D. Schall, Brent A. Vogt, Robert J. Morecraft, Shelley Tischkau, Menno P. Gerkema, Ruud M. Buijs, Alfred J. Lewy, David Hazlerigg, Takashi Yamamoto, Marcelo Epstein, Jürgen A. Ripperger, Urs Albrecht, Achim Kramer, Mario A. Ruggero, Robert V. Shannon, Manuel S. Malmierca, Philip H. Smith, Beate Sodian, Andreas Nieder, Fred W. Mast, Ben Godde, Thorsten Hansen, Karl R. Gegenfurtner, Philippe Faure, Douglas W. Allan, Hideki Asoh, Wilfrid Jänig, Ilya A. Rybak, Jeffrey C. Smith, Amir Karniel, Vittorio Sanguineti, Fiona Mansergh, Jonathan R.Wolpaw, Dennis J. McFarland, Denis Mareschal, Nadja Althaus, Tai Sing Lee, Thomas A. Cleland, Graham C. Goodwin, Arie Feuer, Mark L. Latash, Oscar Marín, Paul J. Lucassen, Karin Boekhoorn, Fiona Francis, Henk J. Groenewegen, Hisashi Ogawa, Vaughan G Macefield, Ingvars Birznieks, and Martin Biel

Published
2009
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41. Functional maturation of the first synapse in olfaction: development and adult neurogenesis

Author

Antoine Nissant, Pierre-Marie Lledo, Kerren Murray, Matthew S. Grubb, Perception et Mémoire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Olfactory system, MESH: Cell Differentiation, Male, MESH: Neurons, Olfaction, Biology, MESH: Animals, Newborn, MESH: Synapses, Synapse, 03 medical and health sciences, Mice, 0302 clinical medicine, Olfactory nerve, MESH: Mice, Inbred C57BL, MESH: Smell, Animals, MESH: Animals, MESH: Neuronal Plasticity, Olfactory memory, MESH: Mice, 030304 developmental biology, Neurons, 0303 health sciences, Neuronal Plasticity, General Neuroscience, Neurogenesis, Cell Differentiation, Articles, MESH: Male, Olfactory bulb, Mice, Inbred C57BL, Smell, Animals, Newborn, Synapses, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Olfactory ensheathing glia, Neuroscience, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; The first synapse in olfaction undergoes considerable anatomical plasticity in both early postnatal development and adult neurogenesis, yet we know very little concerning its functional maturation at these times. Here, we used whole-cell recordings in olfactory bulb slices to describe olfactory nerve inputs to developing postnatal neurons and to maturing adult-born cells labeled with a GFP-encoding lentivirus. In both postnatal development and adult neurogenesis, the maturation of olfactory nerve synapses involved an increase in the relative contribution of AMPA over NMDA receptors, and a decrease in the contribution of NMDA receptors containing the NR2B subunit. These postsynaptic transformations, however, were not mirrored by presynaptic changes: in all cell groups, paired-pulse depression remained constant as olfactory nerve synapses matured. Although maturing cells may therefore offer, transiently, a functionally distinct connection for inputs from the nose, presynaptic function at the first olfactory connection remains remarkably constant in the face of considerable anatomical plasticity.

Published
2008
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42. Réfugiés palestiniens, citoyenneté et État-nation

Author

Stéphane Nissant, Jean-Marck Molignier, and Sari Hanafi

Subjects
General Medicine
Abstract

La globalisation a transformé le rapport des migrants à leur pays d'origine et d'accueil, interrogeant leurs relations d'allégeance et de souveraineté avec un pôle de centralité de la diaspora. L'auteur analyse un exemple emblématique de la façon dont les migrants palestiniens questionnent les notions d' Etat-nation, de frontière et de citoyenneté., Hanafi Sari, Nissant Stéphane, Molignier Jean-Marck. Réfugiés palestiniens, citoyenneté et État-nation. In: Hommes et Migrations, n°1272, Mars-avril 2008. Mondialisation et migrations internationales. pp. 22-43.

Published
2008

44. How Bartter’s and Gitelman’s Syndromes, and Dent’s Disease Have Provided Important Insights into the Function of Three Renal Chloride Channels: ClC-Ka/b and ClC-5

Author

Lourdel, Stéphane, Loffing, Johannes, Favre, Guillaume, Paulais, Marc, Nissant, Antoine, Fakitsas, Panos, Créminon, Christophe, Féraille, Eric, Verrey, François, Teulon, Jacques, Doucet, Alain, Deschênes, Georges, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique [AP-HP Hôpital Européen Georges Pompidou, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire Interdisciplinaire Solidarités, Sociétés, Territoires (LISST), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Medicago Inc., Unité de Néphrologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, and Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-École des hautes études en sciences sociales (EHESS)-École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA)

Subjects
MESH: Rats, MESH: Probability, MESH: Biological Transport, MESH: Puromycin, [SDV]Life Sciences [q-bio], MESH: Rats, Sprague-Dawley, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Sodium Channels, MESH: Hypernatremia, Chloride Channels, MESH: Reverse Transcriptase Polymerase Chain Reaction, Animals, Humans, MESH: Animals, MESH: Epithelial Sodium Channels, MESH: Fluorescent Antibody Technique, MESH: Sodium-Potassium-Chloride Symporters, MESH: Immunoblotting, urogenital system, MESH: Reference Values, Bartter Syndrome, MESH: Sodium-Hydrogen Exchangers, MESH: Sensitivity and Specificity, MESH: Male, MESH: Hyperaldosteronism, MESH: Nephrosis, Kidney Diseases
Abstract

International audience; Chloride channels are expressed in almost all cell membranes and are potentially involved in a wide variety of functions. The kidney expresses 8 of the 9 chloride channels of the ClC family that have been cloned so far to date in mammals. This review focuses on the pathophysiology of two renal disorders that have contributed recently to our understanding of the physiological role of chloride channels belonging to the ClC family. First are the related syndromes of Bartter's and Gitelman's, in which inactivating mutations of the genes encoding either of the ClC-Ks, or their regulatory beta-subunit barttin, have shown the important contribution of these chloride channels to renal tubular sodium and chloride (NaCl) transport along the loop of Henle and distal tubule. Second is the renal Fanconi syndrome known as Dent's disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule. The underlying pathophysiology of this inherited disorder demonstrates how ClC-5 is directly or indirectly required for the reabsorption of filtered low-molecular-weight proteins and bioactive peptides, also expression of membrane transporters, and clearance of calcium-based stone-forming crystals.

Published
2006
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45. Hyperaldosteronemia and Activation of the Epithelial Sodium Channel Are Not Required for Sodium Retention in Puromycin-Induced Nephrosis

Author

Panos Fakitsas, Antoine Nissant, Jacques Teulon, Johannes Loffing, Eric Féraille, Stéphane Lourdel, Christophe Créminon, Marc Paulais, Georges Deschênes, Guillaume Favre, François Verrey, Alain Doucet, Laboratoire de physiologie et génomique rénales (CNRS UMR7134 - Institut des Cordeliers), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Cordeliers [Paris], University of Fribourg, Universität Zürich [Zürich] = University of Zurich (UZH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fondation pour Recherche Médicale [Geneva], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Zurich, Doucet, A, Université de Fribourg = University of Fribourg (UNIFR), and Paulais, Marc

Subjects
Male, Epithelial sodium channel, 10017 Institute of Anatomy, 030232 urology & nephrology, Fluorescent Antibody Technique, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Sodium Channels, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, Reference Values, 0303 health sciences, Hypernatremia, Aldosterone, 2727 Nephrology, Reverse Transcriptase Polymerase Chain Reaction, Reabsorption, General Medicine, respiratory system, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Nephrology, Nephrosis, Puromycin, hormones, hormone substitutes, and hormone antagonists, inorganic chemicals, medicine.medical_specialty, Sodium-Hydrogen Exchangers, Sodium-Potassium-Chloride Symporters, Sodium, Immunoblotting, chemistry.chemical_element, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 610 Medicine & health, 10071 Functional Genomics Center Zurich, Sensitivity and Specificity, 03 medical and health sciences, Internal medicine, Hyperaldosteronism, medicine, Animals, Hyperaldosteronemia, Epithelial Sodium Channels, Probability, 030304 developmental biology, Renal sodium reabsorption, urogenital system, Biological Transport, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Apical membrane, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Rats, Endocrinology, chemistry, 570 Life sciences, biology, U7 Systems Biology / Functional Genomics
Abstract

International audience; Edema and ascites in nephrotic syndrome mainly result from increased Na+ reabsorption along connecting tubules and cortical collecting ducts (CCD). In puromycin aminonucleoside (PAN)-induced nephrosis, increased Na+ reabsorption is associated with increased activity of the epithelial sodium channel (ENaC) and Na+,K+-ATPase, two targets of aldosterone. Because plasma aldosterone increases in PAN-nephrotic rats, the aldosterone dependence of ENaC activation in PAN nephrosis was investigated. For this purpose, (1) the mechanism of ENaC activation was compared in nephrotic and sodium-depleted rats, and (2) ENaC activity in PAN-nephrotic rats was evaluated in the absence of hyperaldosteronemia. The mechanism of ENaC activation was similar in CCD from nephrotic and sodium-depleted rats, as demonstrated by (1) increased number of active ENaC evaluated by patch clamp, (2) recruitment of ENaC to the apical membrane determined by immunohistochemistry, (3) shift in the electrophoretic profile of gamma-ENaC, and (4) increased abundance of beta-ENaC mRNA. Corticosteroid clamp fully prevented all PAN-induced changes in ENaC but did not alter the development of a full-blown nephrotic syndrome with massive albuminuria, amiloride-sensitive sodium retention, induction of CCD Na+,K+-ATPase, and ascites. It is concluded that in PAN-nephrosis, (1) ENaC activation in CCD is secondary to hyperaldosteronemia, (2) sodium retention and induction of Na+,K+-ATPase in CCD are independent of hyperaldosteronemia, and (3) ENaC is not necessarily limiting for sodium reabsorption in the distal nephron.

Published
2005
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46. Exploration of the Basolateral Chloride Channels in the Renal Tubule using

Author

Martine Imbert-Teboul, Pedro Marvao, Stéphane Lourdel, Jacques Teulon, Romain Guinamard, Marc Paulais, Antoine Nissant, Laboratoire de physiologie et génomique rénales (CNRS UMR7134 - Institut des Cordeliers), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Cordeliers [Paris], and Paulais, Marc

Subjects
Physiology, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, chemistry.chemical_element, Calcium, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Chloride, Mice, 03 medical and health sciences, 0302 clinical medicine, Chloride Channels, Physiology (medical), medicine, Animals, Humans, Patch clamp, Distal convoluted tubule, Kidney Tubules, Distal, 030304 developmental biology, Epithelial polarity, 0303 health sciences, biology, Chemistry, urogenital system, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, Cystic fibrosis transmembrane conductance regulator, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Electrophysiology, medicine.anatomical_structure, Nephrology, Chloride channel, biology.protein, Biophysics, Chlorine, Ion Channel Gating, 030217 neurology & neurosurgery, medicine.drug
Abstract

International audience; Chloride channels located on the basolateral membrane are known to be involved in chloride absorption in several parts of the renal tubule, and particularly in the thick ascending limb and distal convoluted tubule. The data available suggest that the ClC-K channels play the major role in this process. We provide here a description of the electrophysiological properties of these channels, still very incomplete at this stage, and we attempt to compare ClC-Ks to three chloride channels that we have identified in the basolateral membrane of microdissected fragments of the mouse renal tubule using the patch-clamp technique. Based on anion selectivity and dependence on external pH and calcium shown by the ClC-Ks, we propose candidate ClC-K1 and ClC-K2 in native tissue. We also discuss the possibility that chloride channels that do not belong to the ClC family may also be involved in the absorption of chloride across the cortical thick ascending limb.

Published
2005
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48. The endocannabinoid system controls food intake via olfactory processes

Author

Soria-Gómez, Edgar, primary, Bellocchio, Luigi, additional, Reguero, Leire, additional, Lepousez, Gabriel, additional, Martin, Claire, additional, Bendahmane, Mounir, additional, Ruehle, Sabine, additional, Remmers, Floor, additional, Desprez, Tifany, additional, Matias, Isabelle, additional, Wiesner, Theresa, additional, Cannich, Astrid, additional, Nissant, Antoine, additional, Wadleigh, Aya, additional, Pape, Hans-Christian, additional, Chiarlone, Anna Paola, additional, Quarta, Carmelo, additional, Verrier, Daniéle, additional, Vincent, Peggy, additional, Massa, Federico, additional, Lutz, Beat, additional, Guzmán, Manuel, additional, Gurden, Hirac, additional, Ferreira, Guillaume, additional, Lledo, Pierre-Marie, additional, Grandes, Pedro, additional, and Marsicano, Giovanni, additional

Published
2014
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49. A Chloride Channel at the Basolateral Membrane of the Distal-convoluted Tubule

Author

Jacques Teulon, Pedro Marvao, Stéphane Lourdel, Antoine Nissant, Marc Paulais, Laboratoire de Physiologie [Institut des Cordeliers, Paris] (CNRS-FRE 2468), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), S. Lourdel holds a PhD fellowship from the Ministère de la Recherche and M. Paulais is an INSERM researcher., Paulais, Marc, Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
Male, chloride channel, kidney, Physiology, Intracellular pH, 030232 urology & nephrology, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, Membrane Potentials, Mice, 03 medical and health sciences, 0302 clinical medicine, Chloride Channels, medicine, Animals, Patch clamp, Distal convoluted tubule, PKC, Kidney Tubules, Distal, Cells, Cultured, Protein Kinase C, 030304 developmental biology, Epithelial polarity, Membrane potential, 0303 health sciences, Chemistry, Cell Membrane, Colforsin, Electric Conductivity, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, patch-clamp, Hydrogen-Ion Concentration, Apical membrane, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, medicine.anatomical_structure, Biochemistry, Chloride channel, Biophysics, Tetradecanoylphorbol Acetate, Calcium, Cotransporter, Ion Channel Gating, ClC-K
Abstract

International audience; The distal-convoluted tubule (DCT) of the kidney absorbs NaCl mainly via an Na+-Cl- cotransporter located at the apical membrane, and Na+, K+ ATPase at the basolateral side. Cl- transport across the basolateral membrane is thought to be conductive, but the corresponding channels have not yet been characterized. In the present study, we investigated Cl- channels on microdissected mouse DCTs using the patch-clamp technique. A channel of approximately 9 pS was found in 50% of cell-attached patches showing anionic selectivity. The NPo in cell-attached patches was not modified when tubules were preincubated in the presence of 10-5 M forskolin, but the channel was inhibited by phorbol ester (10-6 M). In addition, NPo was significantly elevated when the calcium in the pipette was increased from 0 to 5 mM (NPo increased threefold), or pH increased from 6.4 to 8.0 (NPo increased 15-fold). Selectivity experiments conducted on inside-out patches showed that the Na+ to Cl- relative permeability was 0.09, and the anion selectivity sequence Cl(-)--I(-) > Br(-)--NO3(-) > F(-). Intracellular NPPB (10-4 M) and DPC (10-3 M) blocked the channel by 65% and 80%, respectively. The channel was inhibited at acid intracellular pH, but intracellular ATP and PKA had no effect. ClC-K Cl- channels are characterized by their sensitivity to the external calcium and to pH. Since immunohistochemical data indicates that ClC-K2, and perhaps ClC-K1, are present on the DCT basolateral membrane, we suggest that the channel detected in this study may belong to this subfamily of the ClC channel family.

Published
2003
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50. Early synapse formation in developing interneurons of the adult olfactory bulb

Author

Panzanelli, P, Bardy, C, Nissant, A, Pallotto, M, Sassoè-Pognetto, M, Lledo, P M, Fritschy, J M, Panzanelli, P, Bardy, C, Nissant, A, Pallotto, M, Sassoè-Pognetto, M, Lledo, P M, and Fritschy, J M

Abstract

New olfactory bulb granule cells (GCs) are GABAergic interneurons continuously arising from neuronal progenitors and integrating into preexisting bulbar circuits. They receive both GABAergic and glutamatergic synaptic inputs from olfactory bulb intrinsic neurons and centrifugal afferents. Here, we investigated the spatiotemporal dynamic of newborn GC synaptogenesis in adult mouse olfactory bulb. First, we established that GABAergic synapses onto mature GC dendrites contain the GABA(A) receptor alpha2 subunit along with the postsynaptic scaffolding protein gephyrin. Next, we characterized morphologically and electrophysiologically the development of GABAergic and glutamatergic inputs onto newborn GCs labeled with eGFP (enhanced green fluorescent protein) using lentiviral vectors. Already when reaching the GC layer (GCL), at 3 d post-vector injection (dpi), newborn GCs exhibited tiny voltage-dependent sodium currents and received functional GABAergic and glutamatergic synapses, recognized immunohistochemically by apposition of specific presynaptic and postsynaptic markers. Thereafter, GABAergic and glutamatergic synaptic contacts increased differentially in the GCL, and at 7 dpi, PSD-95 clusters outnumbered gephyrin clusters. Thus, the weight of GABAergic input was predominant at early stages of GC maturation, but not later. Newborn GC dendrites first reached the external plexiform layer at 4 dpi, where they received functional GABAergic contacts at 5 dpi. Reciprocal synapses initially were formed on GC dendritic shafts, where they might contribute to spine formation. Their presence was confirmed ultrastructurally at 7 dpi. Together, our findings unravel rapid synaptic integration of newborn GCs in adult mouse olfactory bulb, with GABAergic and glutamatergic influences being established proximally before formation of output synapses by apical GC dendrites onto mitral/tufted cells.

Published
2009

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