Synapses and neural circuits in behaviour
The general aim of the team is to understand how cortical synaptic circuits process and encode sensory and contextual information . We investigate in parallel the CA3 region of the hippocampus and the gustatory cortex (GC). The main strength and originality of our research lies in the systematic back-and-forth interrogation of synapses and circuits ex vivo at a molecular and cellular level, and in vivo in the context of intact neural circuits in behaving mice.
Processing and storage of information depend on multiple mechanisms, from activity-dependent plasticity processes with distinct temporal dynamics to integration of different inputs along the dendritic arborization. We will focus on the mechanisms and integrated consequences of short-term presynaptic plasticity at identified cortical synapses. Presynaptic plasticity occurs within a short- term (seconds to minutes) and long-term (up to hours) time frame at thalamo-cortical and cortico-thalamic synapses, as well as at mossy fiber synapses in CA3. Presynaptic plasticity is postulated to be powerful in controlling synaptic cortical circuits. However direct evidence for a role in controlling sensory and contextual information processing is lacking.
Synaptic alteration is a strong predictor of cognitive decline in Alzheimer’s disease (AD). We propose to explore presynaptic failure as a physiopathological determinant of AD pathology. We will use genetic tools and electrophysiology in mice to better understand the physiological and pathological role of the Amyloid Precursor Protein (APP), a central protein in AD, which is abundantly expressed in presynaptic compartments. In parallel we will implement innovative gene targeting methods applied to human organotypic cortical slices in combination with electrophysiology and high-resolution imaging.
The team has engaged into a translational project targeting aberrantly expressed KARs in temporal lobe epilepsy, in collaboration with Valérie Crépel (Inserm, Marseille). Christophe Mulle is one of the scientific founders of Corlieve Therapeutics (www.corlieve.com), a biotech company which aims at finding new therapies to cure intractable temporal lobe epilepsy. The methodology includes work on acute and organotypic human hippocampal and cortical slices from patients with intractable TLE.
Expertise: Synaptic biology, Hippocampus, Insular cortex, Memory, Sensory processing / Gustation, Alzheimer’s disease, Temporal lobe epilepsy – gene therapy
Techniques: In vivo gene transfer, Ex vivo electrophysiology (patch-clamp recordings), In vivo electrophysiology (patch-clamp, silicone probe recordings), Confocal and two-photon cellular imaging, Optogenetics and chemogenetics, Mouse behaviour
Mots clés
Alzheimer, Assemblées neuronales, Connectivité, Epilepsie, Excitabilité neuronale, Neurophysiologie, Optogénétique, Optogénétique et chemogénétique, Physiologie synaptique, Plasticité des réseaux, Plasticité synaptique, Synapse molecular complexesSelected publications
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GluK2 Is a Target for Gene Therapy in Drug‐Resistant Temporal Lobe Epilepsy
Céline Boileau, Severine Deforges, Angélique Peret, Didier Scavarda, Fabrice Bartolomei, April Giles, Nicolas Partouche, Justine Gautron, Julio Viotti, Haley Janowitz, Guillaume Penchet, Cécile Marchal, Stanislas Lagarde, Agnès Trebuchon, Nathalie Villeneuve, Julie Rumi, Thomas Marissal, Roustem Khazipov, Ilgam Khalilov, Fanny Martineau, Marine Maréchal, Anne Lepine, Mathieu Milh, Dominique Figarella‐Branger, Etienne Dougy, Soutsakhone Tong, Romain Appay, Stéphane Baudouin, Andrew Mercer, Jared B. Smith, Olivier Danos, Richard Porter, Christophe Mulle, Valérie Crépel.
Annals of Neurology. 2023-07-06. 94 (4) : 745-761.
DOI: 10.1002/ana.26723 -
APP accumulates with presynaptic proteins around amyloid plaques: A role for presynaptic mechanisms in Alzheimer’s disease?
Tomàs Jordà‐Siquier, Melina Petrel, Vladimir Kouskoff, Una Smailovic, Fabrice Cordelières, Susanne Frykman, Ulrike Müller, Christophe Mulle, Gaël Barthet.
Alzheimer's & Dementia. 2022-01-25.
DOI: 10.1002/alz.12546 -
The Deletion of GluK2 Alters Cholinergic Control of Neuronal Excitability.
Adam Gorlewicz, Gael Barthet, Stefano Zucca, Peggy Vincent, Marilena Griguoli, Noëlle Grosjean, Grzegorz Wilczynski, Christophe Mulle.
Cerebral Cortex. 2021-11-03.
DOI: 10.1093/cercor/bhab390 -
Impaired plasticity of intrinsic excitability in the dentate gyrus alters spike transfer in a mouse model of Alzheimer’s disease
Nan Jiang, Dario Cupolillo, Noelle Grosjean, Emeline Muller, Séverine Deforges, Christophe Mulle, Thierry Amédée.
Neurobiology of Disease. 2021-03.
DOI: 10.1016/j.nbd.2021.105345 -
Distinctive alteration of presynaptic proteins in the outer molecular layer of the dentate gyrus in Alzheimer’s disease
Hazal Haytural, Tomàs Jordà-Siquier, Bengt Winblad, Christophe Mulle, Lars O Tjernberg, Ann-Charlotte Granholm, Susanne Frykman, Gaël Barthet.
Brain Communications. 2021-04-01. 3 (2)
DOI: 10.1093/braincomms/fcab079 -
Hippocampal mossy fibers synapses in CA3 pyramidal cells are altered at an early stage in a mouse model of Alzheimer’s disease.
Viana da Silva S., Zhang P., Georg Haberl M., Labrousse V., Grosjean N., Blanchet C., Frick A., Mulle C..
Journal of Neuroscience. 2019-03-18.
DOI: 10.1523/JNEUROSCI.2868-18.2019 -
Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity.
Barthet G, Jordà-Siquier T, Rumi-Masante J, Bernadou F, Müller U, Mulle C..
Nat Commun.. 2018 Nov 14. 9 (1) : 4780.
DOI: 10.1038/s41467-018-06813-x -
Operation and plasticity of hippocampal CA3 circuits: Implications for memory encoding
Nelson Rebola, Mario Carta, Christophe Mulle.
Nat Rev Neurosci. 2017-03-02. 18 (4) : 208-220.
DOI: 10.1038/nrn.2017.10 -
Control of spike transfer at hippocampal mossy fiber synapses in vivo by GABAA and GABAB receptor-mediated inhibition
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle.
J. Neurosci.. 2017-01-18. 37 (3) : 587-598.
DOI: 10.1523/JNEUROSCI.2057-16.2017 -
Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells.
Sabine Fièvre, Mario Carta, Ingrid Chamma, Virginie Labrousse, Olivier Thoumine, Christophe Mulle.
Nat Comms. 2016-09-27. 7 : 12738.
DOI: 10.1038/ncomms12738 -
Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors.
Silvia Viana da Silva, Matthias Georg Haberl, Pei Zhang, Philipp Bethge, Cristina Lemos, Nélio Gonçalves, Adam Gorlewicz, Meryl Malezieux, Francisco Q. Gonçalves, Noëlle Grosjean, Christophe Blanchet, Andreas Frick, U Valentin Nägerl, Rodrigo A. Cunha, Christophe Mulle.
Nat Comms. 2016-06-17. 7 : 11915.
DOI: 10.1038/ncomms11915 -
Zinc dynamics and action at excitatory synapses.
Angela Maria Vergnano, Nelson Rebola, Leonid P. Savtchenko, Paulo S. Pinheiro, Mariano Casado, Brigitte L. Kieffer, Dmitri A. Rusakov, Christophe Mulle, Pierre Paoletti.
Neuron. 2014-06-01. 82 (5) : 1101-1114.
DOI: 10.1016/j.neuron.2014.04.034 -
Membrane lipids tune synaptic transmission by direct modulation of presynaptic potassium channels.
Mario Carta, Frederic Lanore, Nelson Rebola, Zsolt Szabo, Silvia Viana Da Silva, Joana Lourenço, Agathe Verraes, André Nadler, Carsten Schultz, Christophe Blanchet, Christophe Mulle.
Neuron. 2014-02-01. 81 (4) : 787-799.
DOI: 10.1016/j.neuron.2013.12.028 -
CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
Mario Carta, Patrizio Opazo, Julien Veran, Axel Athané, Daniel Choquet, Françoise Coussen, Christophe Mulle.
EMBO J. 2013-01-04. 32 (4) : 496-510.
DOI: 10.1038/emboj.2012.334
Team member(s)
Chercheurs, Praticiens hospitaliers...
Ingénieur(e)s, technicien(ne)s
Post-doctorant(s)
Julio Viotti Viotti
Ana Moreira de Sa Moreira de Sa
Vincent Dupuy Dupuy
Avishek Roy Roy
Paola Muttathukunnel Muttathukunnel
Doctorant(s)
Simon Lecomte Lecomte
Olga Barba Vila Barba Vila
Mathilde Tortochot-Megne Fotso Tortochot-Megne Fotso
Bruna Mira Mira
Neuropsychologist(s) and speech therapist(s)
Ingénieur(s) hospitalier(s) et ARC
Adresse :
IINS - UMR 5297 - CNRS - Université de Bordeaux - Centre Broca Nouvelle-Aquitaine - 146 rue Léo-Saignat - CS 61292 CASE 130 - 33076 Bordeaux cedex -France