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Dystrophins In The Nervous System: From Neurophysiology to Molecular Therapy – DYSther
Biotechnologies have open new routes for the treatment of Duchenne muscular dystrophy, but only few studies evaluated the potential of these treatments to correct central dysfunctions in this disease, yet they may lead to severe intellectual and neuropsychiatric disturbances. To target central defec
Molecular and cellular underpinnings of primate cortical precursor identity and behavior: a step towards understanding normal and pathological human cortical development – PRIMACOR
The computational abilities of the primate cerebral cortex are largely determined by the structural organization of areas and cortical layers, including the expansion of the superficial layers of the cortex (supragranulaires layers), whose production is tightly regulated during early prenatal develo
Refining the bioactivity of P42, a hit therapeutic peptide, and developing a combined therapeutic peptide approach for treating Huntington’s Disease. – PEP-FOR-HD
Huntington's disease is a rare neurodegenerative disease but for which no medication, to slow or stop the disease, exists. The expression of mutant Huntingtin (Htt) protein, containing an abnormal expansion of polyQ domain, is responsible for this devastating disease. The expression of mutant protei
Control of sleep-wake cycles by the visual system in Drosophila – ClockEye
Comprendre comment l’horloge est synchronisée par les cycles jour-nuit est un aspect clé de la biologie circadienne et ce projet permettra d'améliorer nos connaissances sur le contrôle des cycles veille-sommeil par la lumière. L'organisation neuronale de l'horloge est assez différente chez les insec
Functional importance of the cortical core in the high density counterstream architecture – ARCHI-CORE
We hypothesize that a cortical core plays an important role in the cognitive architectures supporting conscious processing and certain aspects of multisensory integration. Communication vocalizations and visual face perception show remarkably powerful interactions in both humans and NHP. We undertak
Role of adenosine receptors in synapse stabilization – ADONIS
Synapse stabilization and removal is a key developmental process for neuronal networks to operate optimally. Although stabilization (removal) of active (inactive) synapses is well established, the underlying mechanisms are not fully understood. This project may identify such a mechanism at GABAergic
Spreading of Tau assemblies – SPREADTAU
The study of the brain diseases with protein aggregates also called proteinopathies as Prion disorders, Parkinson’s disease or Alzheimer’s disease has opened new questioning. In fact, aggregation of proteins related to these diseases (PrP, alpha-synuclein, amyloid peptide and Tau) is tightly associa
GABA developmental sequence in autism – DevAutism
The present program is based on 2 closely related discoveries that we have made recently: i) the diuretic, NKCC1 chloride importer antagonist, Bumetanide, that shifts the polarity of GABA from excitation to inhibition, decreases the severity of autism in children (Lemonnier et al., Transl Psych, 201
Optogenetic pharmacology for the precise, biochemical control of cholinergic neuromodulation – Nicopto
Optogenetics is a newly emerging technique, which is revolutionizing neuroscience, by allowing the optical activation or inhibition of specific neurons. Most of the technological developments in optogenetics are based on naturally photosensitive proteins from microbes or plants. Our approach to phot
Role of primary cilium and hedgehog pathway in the development of cortical inhibitory circuits – MIGRACIL
Ciliopathies are human pathologies related to abnormal functioning of the primary cilium located at the surface of most cells of the body. They are characterized by developmental abnormalities and generally affect the brain. They are not necessarily associated with visible structural defects when us
Unraveling the dynamics of hippocampal-cortical interactions during the formation of recent and remote memories: behavioral, cellular, molecular and functional bases – MemoryTrack
A fundamental question in Cognitive Neuroscience lies in understanding how our brain is capable of forming and maintaining enduring memories. In humans, memory for facts and events (declarative memory) is initially dependent on the hippocampus. Multidisciplinary approaches have elucidated crucial ce
Shedding light on hub cell function in vivo – HOLOHUB
If hub neurons are critically involved in hippocampal development, it remains unknown whether the same or functionally similar hub cells orchestrate physiological or pathological network oscillations occurring in the adult brain in specific behavioural contexts. We therefore aim at exploring hub fun
Plasticity of hippocampal CA3 circuits in one-trial memory – Hippencode
The ability to encode memory after a single experience is essential for the survival of higher organisms. There is a general consensus that activity-dependent synaptic plasticity plays a key role in the initial storage of memory in the hippocampus. The CA3 subregion of the hippocampus is involved in
PTSD-like memory: neural system dysfunction and underlying molecular alteration – PTSDMEMO
While for 50 years neuro-psychological studies have significantly contributed to the definition of a precise clinical picture of this disorder, the neurobiological bases of PTSD are poorly understood challenging the development of innovative treatments. A main reason for such situation is the lack,
Postnatal development of the brain oxytocin system and Prader-Willi syndrome. – PRADOX
. . . . Oxytocin (OT) is widely accepted as a prosocial neuropeptide essential to maternal bonding and later on in social interactions. Prader-Willi Syndrome (PWS) is a neurodevelopmental genetic disease and the MAGEL2 gene is the main gene involved in the early feeding behavioral deficit and a
Electrophysiological mapping of networks dynamics in basal ganglia in normal and Parkinsonian conditions using optogenetic control of specific neuronal pathway. – OPTOMAP-Parkin
The objective of our research proposal is to define the causal relationship between synchronized oscillatory activity and motor behavior. We are currently focusing on two specific questions: 1) What are the neuronal circuits necessary and sufficient to the abnormal expression of beta oscillations?
Experience-dependent control of both GABAergic connectivity of oligodendrocyte precursors and myelination in the somatosensory cortex – OLIGOSENSOR
Synapses are not anymore considered an exclusive feature of neurons in the brain. Indeed, oligodendrocytes precursor cells (OPCs), a major source of oligodendrocytes in the developing and adult brain, are also contacted by neuronal synapses throughout the central nervous system. However, the role of
Thyroid Hormone modulation of Oligodendrocyte and Neuronal progenitor commitment – OLGA
Multiple Sclerosis is a neurological disorder of the young adult. Over the past 20 years therapeutic progresses have been accomplished. Unfortunately, current treatment strategies do not stop the progression of demyelination. Even though occurrence of spontaneous remyelination is well documented ove
Neurophysiology of cortical networks modulated by subthalamic stimulation: A comparison between obsessive compulsive disorders and Parkinson’s disease – PHYSIOBS
Obsessive-compulsive disorder (OCD), ranked by the World Health Organization as the tenth most disabling illness, is a neuropsychiatric disease affecting 2.5-3% of the population and characterized by recurrent, persistent thoughts, repetitive compulsive behaviours with chronic evolution with severe
Ventral midline thalamus and systems-level consolidation of spatial memories – THALAME
This project aims at a better understanding of the neurobiological mechanisms by which the reuniens and rhomboid nuclei (ReRh) permit the consolidation of enduring memories. Before being enduring, when still depending on the hippocampus, our memories are labile, sensible to interference, thus fragil
Suboptimality of human decision-making: redefining models of choice in terms of neurobiological constraints – SUB-DECISION
Understanding how we humans make decisions - both individually and collectively - is key to improving human societies and human-environment interactions. Previous research has described human individuals as rational agents capable of perceiving, choosing and acting near-optimally. Departures of huma
Cerebral mechanisms underlying social decision making in humans: Combining computational neuroscience with intracranial recordings and model-based fMRI – BRAINCHOICE
Our social decisions rely on probabilistic knowledge about the possible outcomes of choices and on the intentions and cooperativeness of other individuals. The project BRAINCHOICE seeks a better understanding of the neurobiological basis of social decision-making in humans. It develops a new theore
Boosting up attention – Booster
Attention allows us to select the most relevant information that is captured by our senses for further processing, while setting aside the remaining information. It involves selecting, at any given moment, information in space as well as in time. Adults suffering from hemineglect following a strok
Evolution of axon guidance – AxoDevo
Within the animal kingdom, Bilateria were first recognized by Ernst Haeckel at the end of the XIXth century, as a major crown group on the basis of their bilateral symmetry. In all bilateria, subsets of axons, named commissures, interconnect neurons on both sides of the nervous system. The existence
Inactivation of axonal sodium channels: implications for excitability and synaptic transmission – AXODE
Action potentials are generated in central neurons by the opening of sodium (Na) channels in the axon initial segment. Thus, Na channels are primary determinants of neuronal excitability and alteration in their properties often leads to neurological diseases. Nav channels in the axon display peculia
Molecular and neural implications of the body clock in food addiction: illuminating the avenue against obesity – ADDiCLOCK
Obesity, a current worldwide health problem, is observed probably due to excessive or compulsive eating. The neuronal and molecular mechanisms implicated in “food addiction” are unclear. In the brain, food intake is regulated by two compensatory mechanisms, a homeostatic and a hedonic mechanism. Imp
Neural coding of fear memories formation and extinction in frontal association network of the behaving rodent – FEAR-FRA
The dorsal prefrontal cortex (dPFC) of humans and rodents has emerged as a key structure of fear learning, and its dysfunctions may well be involved in many anxiety-related psychiatric diseases. The goal of FEAR-FRA is therefore to understand how the formation, consolidation and extinction of associ
Early epileptic encephalopathies caused by KCNQ2 mutations : from cellular physiology to therapeutic approaches. – EPI'K
Early onset epileptic encephalopathies are a group of rare and severe diseases of brain development accompanied by recurrent and intractable epileptic seizures. The most common genetic cause is the presence of a mutation in the KCNQ2 gene. This gene encodes a potassium channel subunit. The project c
Dynamic ion selectivity of K+ channels in cell excitability and development – Dynaselect
The potassium channel TWIK1 becomes permeable to sodium in acidic pH, particularly in the endosomal recycling compartment. The transition from a non-selective state at acidic pH to a potassium selective state at neutral pH s slow and reversible. It takes several minutes. The inhibitory (selective fo
Upper Motor Neurons and Amyotrophic Lateral Sclerosis: Contribution, Mechanisms and Therapy – CorticALS
Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset neurodegenerative disease of the motor system, with a prevalence of 2-3/100 000. In spite of intensive research efforts, ALS remains an incurable disease and presents with a very severe prognosis, leading to patient death, usually du
Centrosome, a master regulator of cortical development in health and disease – CREDO
The major goal of this project is to better characterize the centrosome-regulated cellular and molecular pathways that contribute to cortical embryonic neurogenesis in health and disease. Through our research program, we aim to tackle a fundamental issue in the field of neuroscience/neurology and ce
C-Low Threshold mechanoreceptor cells and circuits: from touch to pain modulation – C-LTMR
Pain is a physiological signal that contributes to the protection of individuals from potentially harmful stimuli. In pathological conditions, however, maladaptive plasticity of primary afferent neurons conveying sensory information, or of neuronal networks transmitting this information towards the
Reprogramming reactive astrocytes into GABAergic neurons: a new therapeutical approach of epilepsy – ReprogramEpi
Epilepsy is a major clinical problem and about 30% of epileptic patients suffer from seizures that cannot be controlled with currently available medications. In particular, Mesio-Temporal Lobe Epilepsy (MTLE), the most common form of intractable epilepsies, is characterized by recurrent seizures occ
The neural basis of goal-directed behaviour in Rats – Goal
The objectives of this project are (1) to precise anatomical architecture of the temporo-frontal connexions in order to identify the convergence patterns using retrograde and anterograde labelling (2) to describe the spatial and temporal dynamic of information flows in a decision making task using a
Physiopathology of the Gai/mPins complex in the inner ear – Ghearact
Hearing loss caused by a malfunction of the inner ear is one of the most common birth defects in humans. Our project involves a multidisciplinary approach (genetics, imaging, cell and molecular biology and biochemistry), in order to decode the mechanisms of a signalling pathway involved in a rare co
Role of septal inputs in the properties and function of hippocampal circuits – ROSEPTIN-H
This project combines two research groups with complementary expertise in gene targeting approaches and electrophysiology, in slices and in vivo, and is based on a state-of-the-art, innovative methodology. We will use the exquisite possibilities provided by gene-targeting approaches to selectively i
Distinguishing numerical codes in the human brain with high-field imaging – CODENUM
Previous work from our laboratory had shown that using machine learning methods applied to brain activity patterns of human parietal cortex, it is possible to read out the individual number a subject is seeing and holding in mind, opening up new possibilities for investigating the neuronal basis of