lledo coringer bourgeron maskos digregorio
Director: Pierre-Marie Lledo, Deputy director: Pierre-Jean Corringer

Our research group applies a top-down approach with the aim of understanding the neural and cellular basis of sensory perception, learning, and memory in rodents. We chose the mouse because it learns fast and effectively in spontaneous conditions and under constraint, in laboratory conditions. We try to relate the various levels of analysis to each other by asking the same questions at the behavioral, neural, cellular, and molecular level. We are also interested in the function and regulation of neural stem cells in the adult brain. Fundamental questions are addressed with a view to investigating the mechanisms of neuronal birth, migration, differentiation, and also how new neural cells are integrated into, and contribute to, the function of postnatal circuits involved in olfaction. [Website] [Contact]

Ion channels are specialized proteins which control the transport of various ions across the cell membrane. Our aim is to understand the function of a particular class of ion channels involved in neuronal communication, including nicotinic acetylcholine receptors which mediate important pathways of cholinergic neuromodulation in the brain, GABA-A receptors which mediate the majority of the inhibitory transmission in the brain, and GABA-C and 5HT3 which are involved in many human pathologies, and are the target of important therapeutic drugs including nicotinic derivatives, anxiolytics and anesthetics. By using techniques such as X-ray crystallography and electrophysiology coupled to site-directed mutagenesis we try to determine - at an atomic resolution - their molecular mechanism. [Website] [Contact]

Our group gathers geneticists, neurobiologists and clinicians to explore the relationship between genetics and the susceptibility to psychiatric conditions. We are especially interested on autism spectrum disorders, and our previous studies have revealed the implication of a synaptogenetic pathway including the synaptic cell adhesion molecules NLGN3, NLGN4X, and NRXN1 and the scaffolding protein SHANK3 - all crucial for the maintenance of functional synapses. Our aim is to identify new susceptibility genes within this pathway and to characterize the biological factors that regulate it. We explore the genetic/epigenetic hallmarks of affected individuals using high-throughput genotyping and sequencing-based methods, in combination with clinical, neurobiological and neuroimaging data collected from patients or using cell and animal models. [Website] [Contact]
synapsic pathways

The subject of our entity is the functional analysis of brain circuits with a multi-level approach. Specifically, we aim to understand how nicotine acts on the brain, affects cognition, causes addiction, but also neuroprotection in the case of Alzheimer's and Parkinson's Disease. Our strength lies in the association of different kinds of complementary expertise allowing to address these problems from an integrative point of view. Understanding such phenomena requires the development of new tools, like fibred fluorescence microscopy. Nicotine addiction presents a serious social and public health problem, hence, the identification of the molecular mechanisms and circuits involved in nicotine reinforcement and cognition is urgent. Many aspects of the role of endogenous acetylcholine (ACh) can be targeted by administering nicotine to genetically modified animals (GMAs) and to study their response. [Website] [Contact]

Our aim is to characterize the detailed biophysical and cellular mechanisms regulating information transfer at single synapses, and the spatial and temporal distribution of synaptic integration within single dendrites of neurons within functional networks. To date much of the knowledge of synaptic behavior arises from electrophysiological methods such as patch-clamp. However, the spatial and temporal limitations of these tools preclude a deeper understanding of synaptic function at single synaptic contacts. To overcome these limitations we supplement the classical methods with optical techniques which allow us to use light to monitor and manipulate neuronal function with submicron spatial and submillisecond temporal resolution within brain tissue – we use one and two-photon imaging methods to detect synaptic function using Ca2+ indicators and neuronal integration using optical voltage probes. [Website] [Contact]
Purkinje and granule cells

last update 9 january 2012
ura2182 | institut pasteur | paris, FR
contact: sylviane.guesdon@pasteur.fr