Search

Neurodevelopmental disorders (NDDs) affect ~10% of children and are a source of lifelong handicap. NDDs result from the failure of the brain to develop and mature properly and are characterized by high variability of the clinical picture, even when a genetic cause has been identified, which has hamp

We will decipher the functional anatomy of the understudied “reticular formation” of the lower brainstem, at cellular resolution, with a focus on respiratory circuits and their necessary coordination with non-respiratory ones. We previously showed that many respiratory neurons fall into two large ty

Learning and memory have been traditionally associated to the plasticity of glutamatergic synapses. Recent experimental evidence indicates that GABAergic synaptic strength can also be modified in an experience-dependent manner. Yet, the specific role of inhibitory plasticity in the formation of memo

Individual animals differ in traits and preferences. These differences shape their interactions, their prospects for survival, their susceptibility to diseases but also their response to drugs or treatments modulating neural circuits. While there are some evidences that neurogenesis or neuromodulati

SARABANDe is based on the emergence of a new concept in connectomics: the adult brain constantly rewires with experience. The goal of the present study is to understand how brain rewiring is regulated, how it is relevant for learning and cognition, and how it can be targeted to treat brain disorde

The relationship between the function and connectivity of cortical circuits has been a long-standing theme in neuroscience. Although since decades ago the predominant pathways of cortical information processing in primary sensory area have been described, little is known about how stimulus selectivi

G protein-coupled receptors (GPCRs) are excellent drug targets. Recent data show that GPCRs are not only expressed on the cell surface but also in intracellular compartments where they have important functions. This raises the question of the specific receptor subpopulation to be targeted to achieve

Congenital defects afflict more than 3% of births. These developmental diseases are a major public healthcare burden and today the molecular bases of the tissue-tissue interactions that ensure correct tissue morphogenesis in humans remain largely unknown. This is also the case for three-dimensional

The cerebellum plays a major role in the control, timing and learning of skilled movements. The cerebellar cortex combines multimodal sensorimotor information conveyed by mossy fiber (MF) inputs with internal models of the motor apparatus to precisely time cerebellar output. Our goal is to understan

Cortical development progresses through several stages, including neural proliferation, migration and differentiation. Disrupting the completion of one of these steps often leads to brain abnormalities. Characterizing the molecular controls driving the maturation of cortical progenitors into neurons

Juvenile to adult maturation transition (JMT) is an essential event in the lifespan of any organism, in which sexual and somatic maturation is achieved. In recent years, lots of scientific efforts have focused on understanding the mechanism controlling the onset of puberty since a trend for an earli

Reelin (Reln) is an extracellular matrix protein that has been involved in multiple steps of brain development including neuronal migration, dendritic arborization and synaptogenesis. In humans, homozygous RELN mutations leading to a loss of function lead to lissencephaly and cerebellar hypoplasia.

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease. Its burden on health and society is increasing and no treatment is validated. The study of genetic risk factors allows to identify pathways that may contribute to the pathophysiological process. This project focuses on the role

Background Brain wiring can be perturbed by environmental signals. In particular, prenatal inflammation constitutes a risk factor for neurodevelopmental disorders including Schizophrenia (SCZ) and Autism Spectrum Disorders (ASD). Remarkably, prenatal inflammation in rodents using maternal immune ac

Individuality is the sum of the behavioural characteristics that are unique to us and stable over time. In most animals, individuals display specific unique and stable behavioural characteristics, but those characteristics can be changed by social interactions. An example in our society is “peer pre

Opioids are the gold standard for the treatment of moderate to severe pain. However, sustained exposure to opioids can produce analgesic tolerance and/or hyperalgesia. These effects are known to drastically mitigate their effectiveness requiring increasing the dose. These properties have attracted c

When facing danger, mammals display various fear responses among which an overlooked response is analgesia. Indeed, following fear conditioning, presentation of the conditioned stimulus lead to a reduction in pain sensitivity, a phenomenon known as fear conditioned analgesia (FCA). FCA results from

Regulation of neuronal communication by astrocytes relies on gliotransmitter release. Among others, another intriguing pathway would be the release of extracellular vesicles (among which a sub-catgeory called exosomes). Exosomes are endosomal vesicles used by many cells, including neurons, to commun

For the embryo, building a functional nervous system comprising trillions of specific neurons is a real challenge. The central nervous system (the brain and spinal cord) develops from a simple embryonic structure called the neural tube. This consists of neural progenitor cells that initially divide

The finding that new neurons are generated throughout life in the adult mammalian brain, especially in the dentate gyrus of the hippocampus, has opened novel avenues for brain repair. However a better understanding of the mechanisms that guide the generation and integration of new neurons into the a

Storage and recall of information depend on multiple forms of activity-dependent synaptic and intrinsic plasticity processes with distinct temporal dynamics. Within the hippocampus, a myriad of studies have focused on long-term changes in synaptic efficacy occurring on the postsynaptic side. In cont

Neurons and neuroendocrine cells release neurotransmitters, neuropeptides and hormones through calcium-regulated exocytosis. The ultimate step of exocytosis involves fusion of secretory vesicles with the plasma membrane, leading to the merging of these two compartments. Following exocytosis, the exc

Oxytocin modulates neurophysiological functions as anxiety and pain, notably through its action on central amygdala (CeA). Oxytocin receptors (OTR) are expressed in the lateral CeA (CeL), where their activation leads to an increased firing of GABA interneurons. These neurons directly inhibit project

Circadian clocks are present throughout the living world and control many aspects of physiology and behavior. For example, a brain circadian clock controls sleep-wake rhythms and receives light and temperature information to adapt the behavior to day-night cycles. Alterations of the day-night enviro

Behaviors are generated by neuronal circuits which collect sensory information, process and integrate it to make informed decisions, and implement these decisions at the motor output level. Despite extensive work, understanding this process at the molecular, cellular and circuit level remains challe

The neuromodulator dopamine controls reward, motivation, attention, and motor skills and is implicated in addiction. Dopamine neurons extend their axons in very large areas of the brain, especially in the striatum. However, the molecular and functional properties of dopaminergic terminals have remai

Axonal transport defects are observed in many neurological disorders. Analysis of animal models showed that impaired transport can cause neurodegeneration or impinge on the development of neural circuits. In support of such a role in human, mutations in DYNC1H1, that encodes the heavy chain of dynei

The mesocorticolimbic dopaminergic (DAergic) system originating in the ventral tegmental area (VTA) is involved in many functions such as motivation, decision-making, motor control and reinforcement. Furthermore, many diseases such as schizophrenia, ADHD, hyperactivity, and typically addiction have

Ionotropic GABAA receptors selectively conduct chloride (Cl-) through their pore. The direction of Cl- flux through the channel depends on transmembrane Cl- gradients. Therefore, Cl- homeostasis critically determines the polarity and efficacy of GABAergic transmission in the brain. Epilepsy is ofte

Alterations in synaptic function are involved in neurological disorders such as autism spectrum disorders (ASD) and intellectual disability (ID). Rho GTPase signaling controls the morphogenesis of dendritic spines that support the synapses by regulating actin cytoskeleton dynamics. The Rho GTPase ac