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Regulation of neuronal connectivity by second messengers: decrypting the codes – MessengerCodes
Second messengers and especially cyclic nucleotides – cyclic AMP (cAMP) and cyclic GMP (cGMP) – and calcium are critical modulators of neuronal network development. In the visual system, they are crucial for refinement of the three projection maps of retinal ganglion cells (RGCs) into their main tar
Validation of MT5-MMP as a new therapeutic target in Alzheimer’s disease and mechanisms of action – MAD5
The overall objective of MAD5 is to better understand the proteolytic pathways underlying amyloidogenesis and neuroinflammation in the context of neurodegeneration and cognitive decline in Alzheimer's disease. Both partners have collaborated and published together over the past few years and have ge
Study of hevin's regulation, mode of action and function in the normal and pathological brain: focus on addiction – hevinsynapse
My research project focuses on the role of hevin, a matricellular protein, as a novel molecular mechanism underlying the individual vulnerability to drugs of abuse, in particular cocaine. Matricellular proteins mediate interaction between cells and the extracellular matrix and are essential regulato
Physiopathological regulation of single NMDA receptor dynamics in the hippocampus – DynHippo
Most of the maturation and plasticity of glutamatergic synapses rely on the postsynaptic activation of N-Methyl-D-Aspartate receptor (NMDAR). In addition, a dysregulation of the NMDAR signaling has been proposed to play a direct role in the emergence of neuropsychiatric disorders, such as schizophre
Cajal-Retzius neurons: from migration in the cerebral cortex to the construction of functional and dysfunctional neural circuits – CRsys
The neocortex controls sensory perception, motor behaviors and cognitive functions. These functions rely on a complex architecture of neural networks that begins to be established during embryonic development. This early developmental phase constitutes a major step in the functional emergence of bra
Interaction of BIN1 and Tau: physiological functions and pathological consequences in Alzheimer’s disease. – BINALZ
Our project has the objective to answer to important new questions about BIN1's involvement in the AD process: (i) How are these interactions controlled? (ii) What are the physiological and disease-state consequences of these interactions? (iii) Which partners modulate these interactions and th
Contribution of astrocytes to hippocampal sharp wave ripples – AstroConRipples
The goal of the project is to better understand the mechanisms of regulation of hippocampal ripples in relation to learning requirements. Although ripples and associated replay of neuronal firing patterns have been shown to play a critical role in memory consolidation, how learning modulates ripple
Role of dopamine-glutamate receptor heteromers and downstream nuclear calcium signaling in addiction. – GLAD
Addiction is associated with an imbalance of dopamine (DA) and glutamate (Glu)- mediated transmission in the brain. Current therapeutic approaches aim primarily at modulating the cognate neurotransmitter receptors but loss of efficacy over time and side effects call for alternative strategies. Previ
Understanding the mechanisms of deafness by using intersectional genetics and functional analysis in the mouse – DEAF
The project aims at deciphering the molecular, anatomical and functional properties of distinct auditory neuronal subpopulations in normal and pathological conditions with the long-term goal to characterize the causes of specific types of deafness. Thanks to the availability of several mouse models
Pathophysiological Implication of Sumoylation in Intellectual Disability – SUMO-FXS
Our research plan and synergistic experiments will allow us to assess the physiological relevance of how a defect in the regulation of FMRP sumoylation may lead to FXS. The most striking result obtained so far is the discovery of the functional consequences of FMRP sumoylation in the brain (Khayachi
Functional study of Heparan suflate for oligodendrogenesis during development and repair – SUGAROLG
Multiple sclerosis is a chronic immune mediated disease most often diagnosed in young adults. Clinical symptoms are related to demyelination of nerve fibers in the central nervous system resulting from death of oligodendrocytes. Myelin lesion secondarily leads to axonal degeneration, a crucial step
Study of a putative novel respiratory center – Phox2RESP
This project consists of elucidating the function of a group of neurons, defined genetically in the posterior brain of mammals. More specifically, our study will target a group of neurons in the pons, probably involved in respiration. In previous work on the role of the retrotrapezoid nucleus (RTN)
Unraveling the properties, regulation and role of AMPAR intracellular transport in synaptic plasticity – PAINT
1. Analyze intracellular transport of AMPAR during basal transmission 2. Visualize AMPAR transport in brain slices 3. Find how intracellular transport is modulated during long term synaptic transmission. 4. Characterize the role of AMPAR subunits associated proteins and their phosphorylation in
DIALOGUE BETWEEN PROTEASES AND THE PERINEURONAL NET (PNN): FROM DEVELOPMENT TO ADULTHOOD – P2N2
This project will examine the dialogue between key extracellular proteases (tissue plasminogen activator -tPA, members of the A Disintegrin And Metalloproteinase with Thrombospondin Motifs family -ADAMTS4, 8, 9, and 15 and gelatinases) and the PNN of FS-PV cortical interneurons. Our project aims at
Combining in vivo spectral biphoton imaging, multiparametric cytometry and mouse genetics to characterize neuroinflammation dynamics and function in EAE models. – NeuroInflamDyn
As a model, experimental autoimmune encephalomyelitis (EAE), which recapitulates the pathological hallmarks of MS, is induced in Thy1-CFP//LysM-EGFP//CD11c-EYFP triple mutant reporter mice in which dorso-spinal axons, resident microglia and circulating monocytes fluoresce in different colors. In viv
Neuronal and Astroglial contribution to intellectual disability – NACID
The clinical spectrum of cognitive disorders (CD) varies widely from Intellectual Disability (ID) to Autism Spectrum Disorder (ASD) and is estimated to affect 1-3% of the population. Genetic evidence indicates that one major functional group of CD-related proteins corresponds to proteins that are en
Knock in Mouse Models and The Pathophysiology of Microtubule associated Cortical Development Disorders – KI-Models-MCD
Epilepsy is a chronic neurological disorder that affects more than 50 million people globally, with 50% of patients developing their first seizure in childhood. In approximately 70% of cases the symptoms of epilepsy can be treated with anti-epileptic drugs (e.g. Benzodiazepines), but in the remainin
Role of microRNAs in age-related impairments of social functions – miRNAsandbrainaging
In this project, we seek to address fundamental issues of brain biology, namely, how epigenetic mechanisms contribute to fine-tune brain functions. Accumulating evidences points out that miRNAs might be key players in regulating neuronal activity. However, which miRNAs, at which networks and what ar
A genetic approach to decipher the role of T-type calcium channels in neuropathic pain – Pain-T
The detection and processing of painful stimuli in afferent sensory neurons is critically dependent on a wide range of different types of voltage and ligand gated ion channels, including sodium, calcium, and TRP channels, to name a few. The functions of these channels include the detection of mechan