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Recently, we provided genetic basis to support the conclusion that mitochondrial dysfunction can have a causative effect in motor neuron degeneration. We reported a large family with a mitochondrial myopathy associated with motor neuron disease and cognitive decline looking like frontotemporal demen

Understanding how the perception of an environment emerge from the collective dynamics of the massive assembly of neurons that constitutes the vertebrate brain is arguably one of the most challenging scientific question of our time. The multi-scale nature of the brain allows for several complex proc

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are two fatal adult-onset neurodegenerative diseases with a lifetime risk of 1/1000. Both ALS and FTD patients share a very poor prognosis and limited treatment options. ALS and FTD share common genetic risk factors, and co-occur

Glutamate (Glu) is the main excitatory neurotransmitter in the vertebrate central nervous system. Its effect are mediated by the activation of ionotropic and metabotropic receptor (iGlu and mGlu). Among iGlu, the role of the delta family, and especially of GluD1, in synaptic functions is still undef

As obligatory parasites, viruses have refined diverse strategies aimed at manipulating the host cell physiology for their own benefit. For example, it has been shown that the non-cytolytic persistence of Bornavirus in infected neurons was favored by the expression of a small non-structural 10 kDa vi

Parkinson’s disease (PD) is a major progressive neurodegenerative disorder affecting several regions of the brain, especially the substantia nigra (SN). Although symptomatic treatments are available, there are no protective or curative treatments and diagnosis is established only when degeneration i

Neocortical development requires tightly regulated processes, and perturbations lead to malformations (MCDs). Our groups have demonstrated the importance of the cytoskeleton during these key developmental steps. Recently, Cytoplasmic dynein 1, heavy chain 1 (DYNC1H1) mutations were identified in MCD

The present project focuses on chronic pain. Contrary to acute pain, chronic pain is not serving as a warning signal, as it persists for a long time after the initial affliction, and must be considered as a disease per se. It not only causes physical pain, but also induces severe affective and cogni

Neuronal development and synaptic transmission require the continuous production of secreted trophic factors and transmembrane proteins such as adhesion proteins, neurotransmitter receptors, ion-channels, and thus heavily rely on the secretory machinery: the endoplasmic reticulum (ER) and the Golgi

Wakefulness (WK) is a brain functional state allowing vital behaviors and "higher brain functions" including attentional, emotional and cognitive activities. Present knowledge suggests that the maintenance of this complex brain state requires an ascending activation by a large reticular network incl

The role of early experience to shape neural connectivity has been well demonstrated in sensory systems: during defined time windows called critical periods, neural activity induces structural and synaptic changes that contribute to the functional maturation of brain circuits. These periods of devel

Myotonic dystrophy type 1 (DM1) is the most common form of inherited muscular dystrophy in adults, with a worldwide incidence of 1 in 8000. DM1 is a multisystemic condition that affects many tissues as well as age groups. Compelling clinical evidence demonstrates the impairment of the central nervou

In age-related macular degeneration (AMD), dysfunction of retinal pigment epithelium (RPE) cells causes progressive accumulation of insoluble products at their external side. These deposits decrease RPE cell fitness and their ability to protect photoreceptor cells (PRs), leading to degeneration of P

Because of its prevalence (around 10% in the population) and high levels of morbidity and mortality, alcohol use and related disorders are one of the most detrimental health problems worldwide, associated with a very high social and economical cost. Alcohol use disorder (AUD) is a chronic relapsing

Cerebral communication depends on the transmission of information between neuronal elements at synapses. Such transmission is plastic since its strength can either be potentiated or depressed as an adaptive response to intrinsic and extrinsic changes. As the number of synapses in the brain is huge,

The dynamic regulation of AMPA receptors (AMPARs) nanoscale organization, a glutamate receptor that mediates most fast excitatory synaptic transmission in the mammalian central nervous system, constitutes a major mechanism underlying synaptic plasticity, a fundamental basis of learning and memory. W

Intellectual disability (ID, formerly called mental retardation) is an extremely stigmatizing condition characterized by limitations in cognitive, language and social abilities. It is estimated to involve more than 2% of the general population and requires the extensive use of public health resource

This proposal aims at exploring key molecular mechanisms controlling the wiring of neuronal circuits. A first critical step of this developmental program is axon navigation, during which all populations of projection neurons must extend their axons along very specific pathways to connect their prope

Limited efficacy and adverse side-effects of conventional medications for psychiatric disorders highlight an urgent need to identify modifiable risk and resilience mechanisms to develop novel treatment strategies. In this context, substantial evidence has suggested an implication of a deficiency in

Nicotine dependence is the leading cause of illness and premature death in patients with psychiatric disorders. Smokers who successfully abstain are at increased risk of experiencing a depressive episode when compared to individuals who continue smoking. More severe drug withdrawal episodes have als

Tunneling nanotubes (TNTs) are actin-based fine protrusions connecting cells in culture and represent a novel mechanism of cell-to-cell communication. They have been implicated in many phenomena and diseases including spreading of infection, cancer and neurodegeneration. However, the lack of speci

Brain reward system plays a crucial role to maximize fitness by adapting behavior to environment contingencies (e.g. to optimize food consumption). Deciphering the cellular and molecular mechanisms by which activation of reward circuits leads to long-lasting behavioral adaptations is a major challen

Alzheimer’s disease (AD) is the most common dementia in human and concerns 35 million individuals worldwide. As the population ages and because of the impossibility to diagnose with accuracy the pathology at early stages, there is a pressing need to develop new therapies to attenuate memory impairme

Protein-protein interactions during the secretion of neurotransmitters and local hormones or events downstream of receptor binding are difficult to study in a physiological context in situ. Although many of the players and their interactions are known, the dynamics of interactions within a cell phys

The learning of appropriate defensive behavioral responses to threatening situations relies on highly sophisticated mechanisms requiring a fine balance between memory specificity and generalization. While the memory specificity enables accurate behavioral responses when aversive predicting cues are

After spinal cord injury (SCI) patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (INaP), simultaneously with a disinhibition due to a reduce