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Microglia are the resident macrophages of the brain. They fulfill multiple functions across development and adulthood and under disease conditions. Emerging evidence indicates that microglia display differences in their functions that are not exclusively driven by their milieu, rather by the unique

Neuroinflammatory processes and mitochondrial dysfunction contribute to the pathogenesis of neurodegenerative diseases (e.g. Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer, Huntington). However, the links between the two processes and the precise molecular mechanisms involved are

Neurotrophins (NTs) signaling is essential for neuronal survival and network maintenance. It is mediated by NT binding to its receptor and depends on the directed transport of signaling endosomes from the synapse to the nucleus (eg: BDNF-TrkB signaling endosomes in the corticostriatal circuit). Othe

Long-term potentiation (LTP) of excitatory synapses is widely regarded as a cellular correlate of learning and memory. Among other events, it is accompanied by an increase in the size of the postsynaptic compartment known as dendritic spines. This structural change is driven by remodelling of the ac

The CASHH project aims to characterize the genetic and functional interaction between two genes, CNTNAP2 and SHH, associated with neurodevelopmental disorders (NDDs), respectively autism spectrum disorders (ASD) and holoprosencephaly (HPE). NDDs have complex etiologies, and the genetic alterations i

Because they represent functional nodes of regulation for gene expression, RNA binding proteins are disproportionately associated to NeuroDevelopmental Disorders (NDDs) including Autism Spectrum Disorders (ASD). Understanding how these proteins may have cascading effect on core neuronal functions is

The regulation of proteostasis at synapses is essential for synapse formation, function and plasticity. Deficiencies in this process have been associated with neurodevelopmental disorders. Proteostasis involves the regulation of protein synthesis, trafficking and degradation. Ubiquitination is a key

Neuronal communication at the brain requires a careful orchestration of complex trafficking events at presynaptic sites that translate electrical signals into chemical information through action potential-driven synaptic vesicle exocytosis and neurotransmitter release. However, growing information f

Dopamine (DA) neuromodulation in the brain finely regulates motivation, voluntary movements, reward-based learning and valence coding. Slow metabotropic DA signaling and the lack of characterization of DA synapses favored the hypothesis that DA transmission is volumic. We recently purified DA projec

Locomotion relies on repeated sequences of motoneuron activation and subsequent muscle contractions triggered by a rhythmic central pattern generator (CPG) located in the ventromedial part of the lumbar spinal cord. Despite its crucial role, the exact identity of the cells participating to the spina

The complexity of motor control continues to astonish neuroscientists. While the brain is often seen as the primary controller of movements, recent studies indicate that motoneurons from the spinal cord, which directly control muscles, play a more pivotal role than once believed. These motoneurons e

Information flow through cortical neurons can be decomposed into 3 main steps: 1) encoding (action potential (AP) emission), 2) propagation (travel of AP into the axon) and 3) transmission (synaptic relase). This process is determined by voltage-gated ion channels, myelination and synaptic release p

Exploring the molecular mechanisms that shape functionally distinct neuronal subpopulations is a major challenge for neuroscience. To date, most studies have considered the cholinergic interneurons of the striatum (CINs) as a homogeneous population; consequently, the organizational principles underl

Animals, including humans, primates as well as rodents, often exhibit hesitancy towards consuming new foods due to a lack of information about their safety or toxicity. The initial reluctance is termed taste neophobia, typically a temporary effect that diminishes with repeated exposure as the indivi

Auditory deficits are the most frequent sensory defect currently affecting more than 6% of the world population, and, over 700 million people by 2050 expectedly. While hearing impairment is in most cases linked to defective functioning of the auditory sensory hair cells and results in abnormal audit

Although they mainly affect adults, some neurodegenerative diseases may have a neurodevelopmental origin and remain silent during childhood, adolescence and part of adulthood, thanks to compensatory mechanisms. The first symptoms of the disease would appear following the collapse of these compensato

The overall objective of this proposal is to study the causal link between brain GnRH signaling and the regulation of food intake and energy metabolism, and to explore the therapeutic potential of pulsatile GnRH therapy for the treatment of eating disorders at the preclinical level. To this end, the

Maternal obesity has become a major public health concern. Children born to obese mothers are at increased risk of developing obesity, diabetes, cognitive impairment and reproductive problems. Neurodevelopmental defects in one brain region, the hypothalamus, contribute to the maternal transmission o

The ventral tegmental area (VTA) is a critical brain region involved in processing reward-related stimuli and plays a pivotal role in various neuropsychiatric disorders, including addiction. VTA dopaminergic neurons transition from tonic to burst firing mode in response to sensory cues predicting re

Metabotropic glutamate receptors control the physiology and the plasticity of the synapses. However, their nanoscale sub-synaptic distribution, their co-organization regarding glutamate release site determining their activation, and the relation between their activation and the signaling pathways ac

Nervous system disorders have long been dichotomized between early-onset neurodevelopmental traits and late-onset degenerative phenotypes. However, recent studies unveiled strong molecular and causal links between neurodevelopmental and neurodegenerative conditions, thereby challenging this classifi

Astrocytes are not merely “nurturing” cells for neurons but instead crucial regulators of neuronal activity. They display tailored interactions with neurons in a brain region-specific manner and thus regulate a wide range of behaviors including olfaction, food intake or learning. Surprisingly, the r

The construction of the nervous system requires that the proper number and types of neurons are generated by neural progenitor cells in specific locations, at precise developmental times. Defects in these processes will result in abnormal formation of neuronal circuits with functional consequences t

The mammalian Target Of Rapamycin (mTOR) kinase is a master regulator of cell growth present in every eukaryotic cell, from unicellular organisms to humans. Genetic diseases, such as Tuberous Sclerosis Complex (TSC), leading to the up-regulation of mTOR activity predispose to altered cortical develo

In Bilaterians, the transfer of information between hemispheres is crucial for brain function, particularly for binocular vision. Commissural neurons, connecting both sides of the brain, are essential in this process. Although their existence is well-documented, the complexity of their neuronal comp

Nervous systems are initially overpopulated with neurons. This is followed by a key period of remodeling whereby a subset of inappropriate neurons is removed to optimize function in the adult nervous system. The selection of specific connections for elimination involves an exclusive communication be

Cocaine use is increasing in France and Europe. Approximately 15-20% of cocaine users become addicted, and there is currently no approved pharmacological treatment for this addiction. A critical clinical and societal challenge of cocaine addiction is maladaptive drug-seeking, i.e. seeking drugs wh

Efficient sensory processing is vital for survival, and disruptions in this process often lead to over- or under-responsiveness, commonly seen in neurodevelopmental disorders like autism and ADHD.Iit is crucial to identify and understand the neural circuits and cellular mechanisms involved in sensor

Programmed Cell Death (PCD) is strictly regulated during normal nervous system development to establish appropriate neural architecture, by allowing the generation of the correct numbers and diversity of neurons and glia, from insects to humans. Its dysregulation is associated with neurological dise

In Parkinson’s disease, deep brain stimulation of the subthalamic nucleus (DBS-STN) is an effective treatment but benefits only to 5-10% of patients mostly because of its invasive neurosurgery. It is thus crucial to identify less invasive therapeutic targets that could benefit the greatest number of

Most biological activities follow a nearly-24 hours rhythm entrained to the daily environmental Light/Dark cycle referred to as circadian rhythm. Circadian rhythms are driven by an internal clock. This clock regulates locomotor activity quantitatively, as an ON/OFF switch of movements. Our consorti

Neuronal circuit function is defined by synaptic wiring with subcellular precision, which is itself dependent on the distribution of Neurotransmitter Receptors (NTRs) onto postsynaptic dendritic arbors. However, little is known on the developmental mechanisms that establish synaptic subcellular dist

Hereditary neurological diseases present significant clinical challenges due to overlapping clinical symptoms and extensive genetic diversity, often resulting in complex diagnostic journeys for patients. One common mutational mechanism involves nucleotide repeat expansions, whose prevalence has been

Major depressive disorders (MDD) are the most frequent mental illnesses. Most antidepressants (ADs) increase monoamines but have restricted efficacies (~50%), which can lead to treatment resistant depression (TRD). A potential mechanism underlying both MDD and the effects of ADs is increased levels

How perturbations of ubiquitous subcellular structures affect specific brain functions is a major issue in neurobiology. Primary cilia are widely distributed in the central nervous system, yet their dysfunction in humans leads to specific cerebellar defects in Joubert syndrome, a neurodevelopmental