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Articles, Cellular/Molecular

TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive d-Serine Release

Eiji Shigetomi, Olan Jackson-Weaver, Robert T. Huckstepp, Thomas J. O'Dell and Baljit S. Khakh
Journal of Neuroscience 12 June 2013, 33 (24) 10143-10153; DOI: https://doi.org/10.1523/JNEUROSCI.5779-12.2013
Eiji Shigetomi
1Departments of Physiology and
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Olan Jackson-Weaver
1Departments of Physiology and
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Robert T. Huckstepp
2Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095
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Thomas J. O'Dell
1Departments of Physiology and
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Baljit S. Khakh
1Departments of Physiology and
2Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095
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Abstract

Astrocytes are found throughout the brain where they make extensive contacts with neurons and synapses. Astrocytes are known to display intracellular Ca2+ signals and release signaling molecules such as d-serine into the extracellular space. However, the role(s) of astrocyte Ca2+ signals in hippocampal long-term potentiation (LTP), a form of synaptic plasticity involved in learning and memory, remains unclear. Here, we explored a recently discovered novel TRPA1 channel-mediated transmembrane Ca2+ flux pathway in astrocytes. Specifically, we determined whether block or genetic deletion of TRPA1 channels affected LTP of Schaffer collateral to CA1 pyramidal neuron synapses. Using pharmacology, TRPA1−/− mice, imaging, electrophysiology, and d-serine biosensors, our data indicate that astrocyte TRPA1 channels contribute to basal Ca2+ levels and are required for constitutive d-serine release into the extracellular space, which contributes to NMDA receptor-dependent LTP. The findings have broad relevance for the study of astrocyte–neuron interactions by demonstrating how TRPA1 channel-mediated fluxes contribute to astrocyte basal Ca2+ levels and neuronal function via constitutive d-serine release.

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The Journal of Neuroscience: 33 (24)
Journal of Neuroscience
Vol. 33, Issue 24
12 Jun 2013
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TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive d-Serine Release
Eiji Shigetomi, Olan Jackson-Weaver, Robert T. Huckstepp, Thomas J. O'Dell, Baljit S. Khakh
Journal of Neuroscience 12 June 2013, 33 (24) 10143-10153; DOI: 10.1523/JNEUROSCI.5779-12.2013

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TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive d-Serine Release
Eiji Shigetomi, Olan Jackson-Weaver, Robert T. Huckstepp, Thomas J. O'Dell, Baljit S. Khakh
Journal of Neuroscience 12 June 2013, 33 (24) 10143-10153; DOI: 10.1523/JNEUROSCI.5779-12.2013
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