Neuronal activity drives pathway-specific depolarization of astrocyte distal processes
Neuronal activity drives pathway-specific depolarization of astrocyte distal processes
Abstract Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+ is voltage-dependent, but astrocyte membrane potential (Vm) has been thought to be largely invariant. As a result, these voltage-dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators enabling the measurement of Vm at distal astrocyte processes (DAPs), we report large, rapid, focal, and pathway-specific depolarizations in DAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic glutamate transporters. We find that DAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of sub-cellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction. One Sentence SummaryGenetically encoded voltage imaging of astrocytes shows that presynaptic neuronal activity drives focal astrocyte depolarization, contributing to activity-dependent inhibition of glutamate uptake.
Haydon Philip G、Boyden Edward S、Naskar Saptarnab、Sommer Mary、Cohen Adam E、Dulla Chris G、Armbruster Moritz、Adam Yoav、Garcia Jacqueline、Kim Elliot
Department of Neuroscience, Tufts University School of MedicineDepartment of Brain and Cognitive Sciences, Massachusetts Institute of Technology||Department of Biological Engineering, Massachusetts Institute of Technology||McGovern Institute, Massachusetts Institute of Technology||Howard Hughes Medical Institute, Massachusetts Institute of Technology||Koch Institute, Massachusetts Institute of Technology||Center for Neurobiological Engineering, Massachusetts Institute of TechnologyDepartment of Neuroscience, Tufts University School of MedicineDepartment of Neuroscience, Tufts University School of MedicineDepartment of Chemistry and Chemical Biology, Harvard University||Department of Physics, Harvard UniversityDepartment of Neuroscience, Tufts University School of MedicineDepartment of Neuroscience, Tufts University School of MedicineDepartment of Chemistry and Chemical Biology, Harvard University||Edmond and Lily Safra Center for Brain Sciences, the Hebrew University of JerusalemDepartment of Neuroscience, Tufts University School of Medicine||Cell, Molecular, and Developmental Biology Program, Tufts Graduate School of Biomedical SciencesDepartment of Neuroscience, Tufts University School of Medicine
细胞生物学生理学生物物理学
Haydon Philip G,Boyden Edward S,Naskar Saptarnab,Sommer Mary,Cohen Adam E,Dulla Chris G,Armbruster Moritz,Adam Yoav,Garcia Jacqueline,Kim Elliot.Neuronal activity drives pathway-specific depolarization of astrocyte distal processes[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/2021.07.03.450922.点此复制
评论