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

2013; Society for Neuroscience; Volume: 33; Issue: 24 Linguagem: Inglês

10.1523/jneurosci.5779-12.2013

1529-2401

Eiji Shigetomi, Olan Jackson‐Weaver, Robert Huckstepp, Thomas J. O’Dell, Baljit S. Khakh,

Photoreceptor and optogenetics research

Astrocytes are found throughout the brain where they make extensive contacts with neurons and synapses. Astrocytes are known to display intracellular Ca 2+ signals and release signaling molecules such as d-serine into the extracellular space. However, the role(s) of astrocyte Ca 2+ 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ levels and neuronal function via constitutive d-serine release.