Astrocyte Calcium Signaling Shifts the Polarity of Presynaptic Plasticity

Letellier M(1), Goda Y(2).

Author information:
(1)University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience,
Bordeaux, France. Electronic address: .
(2)Okinawa Institute of Science and Technology Graduate University, Tancha,
Onna-son, Okinawa, Japan. Electronic address: .

Astrocytes have been increasingly acknowledged to play active roles in
regulating synaptic transmission and plasticity. Through a variety of
metabotropic and ionotropic receptors expressed on their surface, astrocytes
detect extracellular neurotransmitters, and in turn, release gliotransmitters to
modify synaptic strength, while they can also alter neuronal membrane
excitability by modulating extracellular ionic milieu. Given the seemingly large
repertoire of synaptic modulation, when, where and how astrocytes interact with
synapses remain to be fully understood. Previously, we have identified a role
for astrocyte NMDA receptor and L-VGCCs signaling in heterosynaptic presynaptic
plasticity and promoting the heterogeneity of presynaptic strengths at
hippocampal synapses. Here, we have sought to further clarify the mode by which
astrocytes regulate presynaptic plasticity by exploiting a reduced culture
system to globally evoke NMDA receptor-dependent presynaptic plasticity.
Recording from a postsynaptic neuron intracellularly loaded with BAPTA, briefly
bath applying NMDA and glycine induces a stable decrease in the rate of
spontaneous glutamate release, which requires the presence of astrocytes and the
activation of A1 adenosine receptors. Upon preventing astrocyte calcium
signaling or blocking L-VGCCs, NMDA + glycine application triggers an increase,
rather than a decrease, in the rate of spontaneous glutamate release, thereby
shifting the presynaptic plasticity to promote an increase in strength. Our
findings point to a crucial and surprising role of astrocytes in controlling the
polarity of NMDA receptor and adenosine-dependent presynaptic plasticity. Such a
pivotal mechanism unveils the power of astrocytes in regulating computations
performed by neural circuits and is expected to profoundly impact cognitive
processes.

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Conflict of interest statement: Declaration of Competing Interest The authors
declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.

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