Our lab combines genetics, biophysics, physiology & behavior to understand how sensory inputs are integrated in the spinal cord during development and active locomotion. The lab discovered that neurons contacting the cerebrospinal fluid (CSF) in the spinal cord are mechanoreceptors detecting curvature of the spinal cord and CSF flow, which modulate the activity of spinal neurons controlling locomotion and posture. We use the transparent zebrafish larva to implement optical methods for manipulating and monitoring neuronal activity in motion. Our work aims to unravel the mechanisms by which interoceptive sensory inputs are integrated throughout life to form the spinal cord, and insure homeostasis in the mature stages. Multiple researchers steer basic science and translational projects in the team:

Dr. Claire Wyart is a INSERM director of research (DR1 equivalent to Associate Professor) and led the team since 2011. Eager to quantify neuronal communication dynamically, Claire pursued undergrad studies in STEM and graduated in 2000 from the École Normale Supérieure d'Ulm, Paris. In 2003, he completed a PhD in a physics laboratory at the University of Strasbourg where she developed fluorescent recordings of neuronal network activity. Moving to UC Berkeley for her postdoc in 2005, she was one of the first to use light to manipulate the activity of neurons in vivo. As a pioneer in the emerging field of optogenetics, she used this approach to discover a novel sensory system within the spinal cord. In 2011, Claire starts her team at the Paris Brain Institute: her interdisciplinary group shows that the sensory system she discovered in the spinal cord detects curvature of the spine to optimize the speed and posture during movements. Together, they uncover that this system also controls morphogenesis of the body axis throughout life, and is activated during infection of the central nervous system to enhance innate immunity. Leveraging the transparency of larval zebrafish, her signature lies in deploying cutting-edge optical technologies to investigate neural activity throughout the body during movement, yielding insights into the structure of sensory and motor circuits in vertebrates. Claire is deeply committed to science outreach and training of young researchers in science: https://zenith-etn.com. Claire Wyart's contributions have earned her international recognition, including the Robertson Prize from the New York Stem Cell Foundation (NYSCF, 2016), membership of the European Molecular Biology Organization (EMBO, 2019) and the Richard Lounsbery Prize awarded by the French and American National Academies of Sciences (2022).

Dr. Feng Quan is a project manager who supervises molecular/cellular engineers in the lab : she is an expert in CRISPR-Cas genome editing for knock-in and knock-out, and molecular techniques to investigate interoception in the context of spinal cord injury.

Dr. Kevin Fidelin is a project manager who supervises coding & imaging engineers in the lab: he is an expert in in vivo electrophysiology, functional optogenetics and dynamic population imaging to investigate the structure and functions of motor nuclei in the brainstem.

Prof. Hugues Pascal-Moussellard is a MD/PhD and surgeon in charge of the orthopedic department of the Pitié-Salpêtrière hospital in Paris 13. He conducts with Dr. Laura Marie Hardy, Dr. Thomas Courtin and Prof. Alexis Brice a project aiming to decipher mutations associated with idiopathic scoliosis in humans. In particular, the SCOGEN project relies on Dr. Laura Marie-Hardy, a MD PhD and surgeon head of clinics in the orthopedic department of the Pitié-Salpêtrière hospital. Dr. Marie-Hardy is involved in a scoliosis project to identify genes involved in idiopathic scoliosis in humans in collaboration with Serge Zakine, as well as spinal cord injury.

research

Neuromodulation in the hindbrain and spinal cord

Arousal locomotion is strongly modulated by our inner physiological states. This spontaneous exploratory locomotion reflects the excitability of motor circuits in the spinal cord as well as descending commands from the brain, in particular from the hindbrain. The underlying mechanisms controlling the occurrence of spontaneous locomotion and its natural variability among animals and across physiological states within one animal are not well understood. On one end, we are interested in probing neuromodulatory pathways in the hindbrain and spinal cord for setting the frequency of occurrence of locomotion in the context of circadian rhythm, inflammation and feeding. On the other, we investigate how neuromodulation can influence morphogenesis.

Modulation of motor circuits via the cerebrospinal fluid

The classical view of spinal cord physiology relies on the fact that motor functions are carried by ventral spinal cord while dorsal spinal cord integrates sensory inputs from the periphery. Up to recently, there was no evidence that the vertebrate spinal cord hosts sensory cells conserved throughout vertebrates. Our team has shown evidence for a central sensory motor loop localized in the spinal cord and modulating circuits underlying locomotion and posture. We have evidence that the morphology and molecular markers of this central sensory system is conserved in the mammalian spinal cord. This axial sensory system modulates locomotion, posture, innate immunity and morphogenesis.

Sensory integration in hindbrain and spinal cord throughout life

The contribution of mechanosensory feedback to active locomotion and the nature of underlying spinal circuits remain elusive. We investigate how mechanosensory feedback shapes active locomotion in the zebrafish larva. We find that mechanosensory feedback enhances the recruitment of motor pools during active locomotion. We show that inputs from glutamatergic mechanosensory neurons increase locomotor speed by prolonging fast swimming at the expense of slow swimming during stereotyped acoustic escape responses. The interoceptive sensory integration we have discovered is critical throughout life for growing and maintaining a straight body axis. Altogether, our efforts reveal the basic principles and circuit diagram underlying the modulation of movement, posture and morphogenesis by adjusted mechanosensory feedback in the vertebrate spinal cord.

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Address

Wyart Lab

Spinal Sensory Signaling

I.C.M.

47, bld de l'hopital

Paris 75013 - FRANCE

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