Sensory Disorders

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Department of Neurosciences

Aziz El-Amraoui - Progressive sensory disorders, pathophysiology and therapy

Hearing and vision are essential for every significant activity of daily life, ranging from social interactions and mobility to an appreciation of music, art, and nature. Because of their high prevalence, untreated decline of these sensory deficits has a vast economic & societal impact, impeding communication, later leading to social isolation, depression, reduced physical and cognitive functions. Current team focus is on late onset and/or progressive forms of hearing impairment, combined or not with balance and vision deficits. More specifically, our aims include: i) understand how, despite constant use from birth onwards, our eyes and ears continue to ensure, at least for 5-6 decades, normal vision and hearing, ii) elucidate precise pathogenic features of the human neurosensory disorders using cell- and animal-based models, iii) document how external cues impact sensory decline, and iv) Evaluate and validate in vivo the delivery and efficacy of gene therapies to restore normal senses.

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Pierre-Marie Lledo - How experience and time shape brain circuits

The Lledo laboratory has developed a multi-scale approach to understand the function and the plasticity of neuronal circuits involved in sensory perception, memory and mood control. In particular, researches are aimed at the interface between neuroscience and behavioral science to elucidate complex neural systems underlying behaviors. The team gathers neuroscientists, psychiatrists, and computational scientists to combine modern neurophysiological techniques —in vitro and in vivo awake electrophysiology, optogenetics, awake 2-photon imaging, deep-brain fiber photometry— with behavioral analysis (both human and mice) and theoretical modeling in order to monitor and manipulate neuronal circuits during behavior and in pathological contexts. The team has solid expertise in animal models and behavior, having developed a wide range of behavioral tests to evaluate sensory modalities, mood states, cognitive functions and social interactions. The scientists visualize the dynamic re-wiring of connections (triggered by adult neurogenesis) in mouse models to provide further insight for translational research into mood disorders or viral infections.

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Christine Petit (and the Hearing Institute) - Hearing and associated disorders, from mechanisms to treatment

Exploring the neuronal network functional connectivity of auditory central pathways and cortices, associated plasticity and multimodal sensory integration as well as how they are altered by hearing deficits of genetic and non-genetic origins including those present in schizophrenia and autism... Understanding the link between auditory impairment and dementia (Alzheimer), with prospects of prevention and curing. Noise-Induced Hearing Loss, the major environmental cause of hearing loss and presbycusis (age-related hearing impairment): development of corresponding biomarkers for multiparametric diagnosis (innovative audiometric tests, brain imaging, psychoacoustics, genomics, epigenomics, other biological markers with integration by Artificial Intelligence), rationalization of clinical trials (stratification of populations) for the testing candidate therapeutic agents and search for new therapeutic agents. Gene therapy for curing monogenic severe to profound deafness. The strategy is based on a continuous back and forth movement between patients and animal models. Collaborative works in perspective with the Immunology Department.

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Department of Virology

Monique Lafon - Pathology of viruses that target the nervous system

Research in the Viral NeuroImmunology Laboratory aims to establish the molecular basis for the pathogenicity of viruses that infect the nervous system, such as rabies virus. The team has discovered this virus has the intriguing property to promote the survival of the neurons it infects. Elucidation of the mechanisms of action and identification of the critical domain of the viral protein that controls survival have resulted in the development of a new drug candidate for the treatment of neurodegenerative diseases such as retina diseases or Amyotrophic Lateral Sclerosis (Charcot Disease).

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