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Optical control of synaptic function via adhesion molecules – SyntheSyn
Elucidation of the complex map of neural connectivity in the mammalian brain has become one of the major goals of modern neuroscience. Fundamental to such efforts, and to the comprehension of neurological disorders, is to gain an understanding of the mechanisms that wire up, sculpt and maintain syna
Role of TSHZ3 in the development and function of neuronal systems involved in autism spectrum disorder – TSHZ3inASD
Autism spectrum disorder (ASD) defines a heterogeneous group of neurodevelopmental disorders that share core behavioral abnormalities, characterized by impairments in social communication and interaction, restricted interests and repetitive behaviors. ASD has a large genetic component and integrativ
NEDD4L-mediated ubiquitination activity and AKT-mTOR pathways deregulation in malformations of cortical development – MCD-NEDD4L-mTOR
The development of the human cerebral cortex requires coordinated spatial and temporal regulation of interdependent developmental processes that include proliferation, migration and layering, as well as differentiation of distinct neuronal populations. Disruption of any of these processes can result
Control of synaptic plasticity by microglia: a night job ? – Micromem
Brain plasticity that underlies memory function likely results from a balance between synapse formation, potentiation and removal. The synapse formation and potentiation occur mostly during wakefulness, while synaptic downscaling and removal take place mostly during sleep. Immune signaling molecules
Function of Meteorins in commissural axon guidance – MetAxon
In most animal species characterized by an almost perfect symmetry along the anteroposterior body axes, commissural axons connect neurons on the left and right side of the nervous system. This communication at the level of the two brain hemispheres and the two sides of the spinal cord is necessary f
Development and Physiology of the Intrinsic Neurons of the Heart – HEARTBRAIN
The heart functions under dual autonomic modulation, sympathetic and parasympathetic. A classical view has been that autonomic ganglia serve as simple relay stations for two antagonistic influences on the heart: stimulating through the sympathetic outflow, inhibiting through the parasympathetic outf
Dynamics Of REMYelination: study of nodes of Ranvier reassembly and its impact on repair – DOREMY
Myelination of axons is an essential step to ensure the rapid propagation of action potentials by saltatory conduction, a mechanism that relies on the nodes of Ranvier. These short unmyelinated axonal domains are highly enriched in voltage-gated sodium channels (Nav), which allow the regeneration an
Pathological mechanisms underlying microcephaly Role of centrosomes and primary cilia in cerebral cortical development – CentrosomeCiliaMicroceph
Malformations of Cortical development (MCD) constitute a wide spectrum of brain disorders representing a major cause of intellectual deficiency and epilepsy. Among them, microcephaly (MIC) is characterized by prenatal reduced brain size occurring both isolated and in association with other MCD inclu
Contribution of IP3Rs and endoplasmic reticulum to Ca2+ signalling in astrocytes – CASTRO
Research on glia cells, in particular astrocytes in the brain, has in recent years led to a thorough reappraisal of their role for brain functions, extending greatly beyond the classic view as mere providers of structural and nutritional support to neurons. The concept of the “tripartite synapse”, c
Role of C9ORF72 in Amyotrophic Lateral Sclerosis – C9ORF72-ALS
Amyotrophic Lateral Sclerosis (ALS) is the third most common neurodegenerative disease in the western world, affecting 1 individual in 50,000 people. This devastating disease is characterized by degeneration of motor neurons leading to muscle wasting and weakness, ultimately resulting in paralysis a
RETICULOSPINAL NEURONS IN MOTOR CONTROL – MotorV2
This project aims at deciphering the function of genetically-defined groups of neurons in the central nervous system, with cutting edge tools that are increasingly applied to interrogate the neuronal basis of behavior. More specifically, it will explore clusters of brainstem neurons in motor control
Identification of functional microRNA/mRNA complexes in the mouse brain: From neurogenesis to behavior and pathology – MicroRNAct
microRNAs (miRNAs) are key regulators of brain development and function, controlling processes like neural stem cell determination, proliferation, migration and integration. Moreover, synapse stability and plasticity are regulated by local interactions between miRNAs and target mRNAs. Analysis o
Detection of bacteria by neurons: modalities and consequences for fly behaviour – BACNEURODRO
Since eukaryotes live in an environment heavily contaminated by microorganisms, it is not surprising that they have forged, over the times, extremely complex and intimate relationships between them. It also expected that eukaryotes have developed mechanisms to perceive the presence of bacteria and t
A single-laser source all-optical holographic microscope for brain investigation – SLALLOM
Optical means for stimulating and monitoring neuronal activity have provided a lot of insight in neurophysiology lately toward our understanding on how brain works. Optogenetic actuators, calcium or voltage imaging probes and other molecular tools combined with advanced microscopies allowed ‘all-opt
The molecular mechanisms underlying the transition from acute to chronic pain! Insights from an unconventional Myosin protein – Myochronic
Transition from acute to chronic pain represents a major medical problem worldwide. Its impacts on health care costs and social lives of patients are dramatic. Chronic inflammatory, neuropathic or postoperative pain occurs as a consequence of aberrantly prolonged sensitization of pain pathways both
Synaptic basis of predictive coding in the cerebellar cortex – SynPredict
An essential feature of the brain, for its interaction with the world, is its ability to predict immediate future and continuously update internal representations. The cerebellum is often viewed as a structure in which predictions can be efficiently generated and updated for use by other brain regio
Chronic JOINT PAIN: Toward new molecular targets. – JOINT-PAIN
Chronic joint pain is a major health problem representing an economic burden for the society. A recent Inserm survey reports that 93% of the French citizens have already suffered from joint pain, with half suffering at the time of the survey. However, joint pain remains poorly relieved by current an
LATE ONSET HEARING IMPAIRMENT: FROM DISEASE MECHANISMS TO THERAPY – HearInNoise
Hearing impairment, the most frequent sensory deficit, causes communication difficulties, often associated with social isolation, depression and reduced physical and cognitive function, with a dramatic economic impact on healthcare systems worldwide. Whatever the cause, genetics, environmental facto
Human Polymorphisms in Nicotinic Receptor Genes---Modeling their role in nicotine dependence and co-morbidities using transgenic rats and mice – SNP-NIC
There is very robust human genetic evidence confirmed by meta-analysis of Genome-Wide Association Studies (GWAS) that human single nucleotide polymorphisms (SNPs) in the CHRNA5/CHRNA3/CHRNB4 cluster on chromosome 15q are linked to smoking risk, the age of initiation, the number of cigarettes smoke
Hormone-related aging and dementia – GRAND
Developmental deficits in cognitive function and dementia create a high medical, emotional and economic burden for society. Over 25 million people suffer from dementia worldwide; with one new case diagnosed every 7 seconds. On the other end of the age spectrum, 3-8% children in Europe and USA suffer
Roles of unconventional GluN3A-containing NMDA receptors in adult brain function – GluBrain3A
In this project we propose to explore, using a multilevel approach, the role of unconventional NMDA receptors (NMDARs) in specific regions of the adult brain involved in higher cognitive functions. Much is indeed known about the central role of the family of conventional GluN1/GluN2 NMDARs in gl
5-HT6 receptor-operated mTOR signaling as a target for disease modifiers to prevent onset of cognitive deficits in schizophrenia. – StopSero6TOR
Schizophrenia is a devastating mental disorder of neurodevelopmental origin, which affects ~1% of the population worldwide and represents a major socio-economic burden. It is characterized by a broad pattern of cognitive symptoms, including decreased attention, impaired memory, inaptitude to solve p
Local control of Endocytosis in neuronal dendrites analysed with new optical Probes – LocalEndoProbes
One of the central problems in neurobiology, and perhaps in all biological systems, is to understand how nerve cells are organised in a network which is both stable and capable of a great plasticity. In particular, synapses are very stable structural elements which can be modified in a few minutes t
The study of axonal physiology in adult cerebellar interneurons – AxonalPhysiology
In the commonly accepted view of synaptic integration, synaptic signals are collected in the somatodendritic domain and summed in the axon initial segment, giving rise to an all-or-none response, the action potential, that is transmitted along the axon and triggers a new wave of transmitter release
The 5-HT6 receptor-associated signalling network in neuronal development – Sero6Dev
Cognitive symptoms accompanying neurodevelopmental pathologies such as schizophrenia or autism spectrum disorders are highly debilitating and current treatment options fail to alleviate them. Accordingly, there is an urgent need for new therapeutic approaches. It has become clear in the last few yea
Nanoscale cellular and molecular fingerprints of synaptic diversity – NanoSYNDIV
Functional synaptic diversity is critical for routing and encoding sensory information in the brain. Yet, the molecular and biophysical underpinnings of such diversity remain unexplored. We hypothesize that nanoscale variations in the number and location of active zone scaffold proteins, as well as
Paradoxical sleep disentangled – PARADOX
Paradoxical sleep (PS) and wakefulness (WK), while fundamentally different consciousness states, are characterized by similar EEG patterns. Here, we aim to disentangle this paradox by investigating the differences in sensorimotor integration between PS and WK using the somatotopically highly organiz
LGI1-mediated modulation of neuronal excitability – LoGIK
Our proposal addresses the question of how LGI1, an extracellular protein secreted by neurons and involved in neurological diseases such as epilepsies or limbic encephalitis, controls intrinsic neuronal excitability and synaptic transmission through the regulation of Kv1 channel expression in the ax
Pharmacogenomics identification of small bioactive molecules for promoting oligodendrogenesis in a model of neonatal brain injury. – NeoRepair
Preterm birth is a public health concern, with many surviving children developing cognitive and behavioral deficits implying a strong social and economic burden for society. Both in humans and rodents, the developmental period around birth is a time of active generation of oligodendrocytes, myelinat