Synaptic circuits of memory
Circuits synaptiques de la mémoire
The team aims at characterizing the function and dysfunction of synaptic transmission and circuits in the central nervous system. The projects have a strong focus on the CA3 region of the hippocampus, which is key for the initial steps in episodic and spatial memory encoding. A majority of projects relate to the less well characterized presynaptic plasticity mechanisms, in relation to the activity of neural circuits and memory encoding. The team combines molecular, cellular and circuit level approaches in physiological conditions as well as in relation to Alzheimer disease.
- Presynaptic plasticity We hypothesize that structural and functional plasticity on the presynaptic side, acting in a concerted fashion, shape the dynamics of neural processing in cortical circuits, which ultimately underlies mechanisms of information processing in the context of memory encoding and sensory perception. We interrogate the molecular mechanisms of presynaptic facilitation at excitatory and inhibitory synapses. We characterize the role of mitochondria and mitochondria-ER contacts in presynaptic mechanisms. We explore the consequences of presynaptic facilitation in the operation of CA3 circuits and memory encoding.
- Operation and plasticity of CA3 circuits. Using electrophysiological and live imaging methods in vitro and in vivo, combined with gene transfer techniques and novel optogenetic toolkits, we characterize the mechanisms of synaptic specification and plasticity within CA3 circuits. We develop parallel methods to interrogate the relationship between the intracellular dynamics of CA3 pyramidal cells in mice, brain states and memory encoding. We have for instance discovered that within theta, an activity and memory related brain state, a majority of CA3 pyramidal cells hyperpolarize, creating the neuronal context for the emergence of engram cells.
- Alzheimer disease (AD) and synaptic physiopathology. During the past years, the team has characterized the impairment of intrinsic and synaptic plasticity in DG and CA3 cells in mouse models of AD. We explore the physiological role for presenilin and APP in presynaptic mechanisms at excitarory and inhibitory synpases and in synapse function. We develop and use models for assessing the role of pathological Tau in the alteration of synaptic circuits in organotypic cultures, including the role of mitochondria.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Membres de l'équipe
Personnel(s) de recherche
IINS - UMR 5297 - CNRS - Université de Bordeaux - Centre Broca Nouvelle-Aquitaine - 146 rue Léo-Saignat - CS 61292 CASE 130 - 33076 Bordeaux cedex -France