PT  - JOURNAL ARTICLE
AU  - Shigetomi, Eiji
AU  - Jackson-Weaver, Olan
AU  - Huckstepp, Robert T.
AU  - O'Dell, Thomas J.
AU  - Khakh, Baljit S.
TI  - TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive <span class="sc">d</span>-Serine Release
AID  - 10.1523/JNEUROSCI.5779-12.2013
DP  - 2013 Jun 12
TA  - The Journal of Neuroscience
PG  - 10143--10153
VI  - 33
IP  - 24
4099  - http://www.jneurosci.org/content/33/24/10143.short
4100  - http://www.jneurosci.org/content/33/24/10143.full
SO  - J. Neurosci.2013 Jun 12; 33
AB  - 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.