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Dual Electrophysiological Recordings of Synaptically-evoked Astroglial and Neuronal Responses in Acute Hippocampal Slices
Published on: November 26, 2012
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Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes
Moritz Armbruster1, Saptarnab Naskar2, Jacqueline P Garcia2,3
1Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA. Moritz.Armbruster@tufts.edu.
Nature Neuroscience
|April 28, 2022
Summary
Large depolarizations in astrocyte processes during neuronal activity were discovered. This astrocyte membrane potential change inhibits glutamate clearance, enhancing neuronal activation and revealing new astrocyte-neuron interactions.
Area of Science:
- Neuroscience
- Cell Biology
- Glial Cell Biology
Background:
- Astrocytes, a type of glial cell, regulate the neuronal synapse environment by clearing glutamate and potassium (K+) from the extracellular space.
- Astrocyte clearance functions are voltage-dependent, yet astrocyte membrane potential (Vm) has been considered largely invariant, limiting the functional relevance of these dependencies.
- Previous understanding did not account for dynamic Vm changes in peripheral astrocyte processes (PAPs).
Purpose of the Study:
- To investigate the dynamic changes in astrocyte membrane potential (Vm) at peripheral astrocyte processes (PAPs) during neuronal activity.
- To determine the mechanisms driving astrocyte depolarization and its functional consequences on glutamate clearance and neuronal activation.
- To characterize a novel class of subcellular astrocyte membrane dynamics and astrocyte-neuron interactions.
Main Methods:
- Utilized genetically encoded voltage indicators for in vivo measurement of Vm in mouse PAPs.
- Recorded Vm changes in PAPs during defined patterns of neuronal activity.
- Assessed the impact of PAP depolarization on astrocyte glutamate clearance capacity and subsequent neuronal activation.
Main Results:
- Observed large, rapid, focal, and pathway-specific depolarizations in PAPs correlating with neuronal activity.
- Demonstrated that these astrocyte depolarizations are driven by presynaptic action potential-mediated K+ efflux and electrogenic glutamate transporters.
- Found that PAP depolarization significantly inhibits astrocyte glutamate clearance, leading to enhanced glutamate-mediated neuronal activation.
Conclusions:
- Astrocyte peripheral processes exhibit significant, activity-dependent voltage dynamics (depolarizations).
- These depolarizations, driven by K+ and glutamate transport, modulate astrocyte function by impairing glutamate clearance.
- This study reveals a novel mechanism of astrocyte-neuron communication where astrocyte membrane potential directly influences synaptic transmission and neuronal excitability.
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