Speakers > Remi BosRemi Bos Institut de Neurosciences de la Timone, Marseille, France
Rémi Bos obtained his PhD in France in 2012 and moved to the U.S. at UC Berkeley for a post-doctoral fellowship. He came back to France in 2016 at INT where he has been recruited as a CNRS permanent researcher since 2018. His main scientific interest is to understand the plasticity of the spinal motor networks from the cellular levels to the behavioral aspects. His research focuses on the Neuron-Glia crosstalk in the spinal motor network. He is trying to understand how astrocytes (1) detect and respond to environmental cues and (2) modify the neuronal excitability both in development and in certain pathological conditions (i.e. following spinal cord injury, multiple sclerosis). To tackle this question, he uses patch-clamp recordings, two-photon calcium imaging, sc-RTPCR and genetic tools to record/modify the astrocytic activity and to observe the influence on (1) neuronal firing properties and (2) muscular activities (i.e. EMG recordings).
Astrocytic contribution to neuronal rhythmicity in the spinal locomotor network
Neuronal rhythmogenesis in the spinal cord is correlated to variations of the extracellular K+ concentration ([K+]e). The [K+]e homeostasis is mainly mediated by astrocytes. Though it is stated that astrocytes compute neuronal information, it is yet unclear how neuronal oscillations are influenced by the astrocytic K+ homeostasis. Here we identify the astrocytic inward-rectifying K+ channel Kir4.1 (a.k.a. Kcnj10) as a key molecular player for neuronal rhythmicity in the spinal central pattern generator (CPG). By combining two-photon calcium imaging with electrophysiology, immunohistochemistry and genetic tools, we report that astrocytes display Ca2+ transients before and during oscillations of neighbouring neurons. The prevention of the astrocytic Ca2+ transients with BAPTA decreases the barium-sensitive Kir4.1 current responsible of the K+ uptake. We then demonstrated in mice that Kir4.1 decrease progressively prevents the neuronal oscillations and alter the locomotor pattern resulting in lower motor performances in challenging tasks. Despite decades of scientific research, the cellular mechanisms responsible of the synchronized rhythmic oscillations driving locomotion are incompletely understood. So far it was known that locomotion is correlated to extracellular K+ changes in the spinal network and that astrocytes are the main regulators of extracellular K+. Recent studies have also highlighted a contribution of gliotransmission in locomotion. Our study represents a significant breakthrough by designating the astrocytic K+ uptake as a key component for synchronizing neuronal rhythmicity and influencing the locomotor pattern at the cellular, microcircuit and system levels. We then offer a better mechanistic understanding of the spinal neuron-astroglia dialogue. Since brain disorders and neurodegenerative diseases have been associated with defective astrocytic function, our data also broaden the spectrum of therapeutic targets for restoring compromised neuronal network excitability. |
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