title: TRPA1 channels are regulators of astrocyte basal calcium levels and long-term potentiation via constitutive D-serine release.
abstract: 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.
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shigetomi
authors.forename: Olan
authors.initials: O
authors.lastname: Jackson-Weaver
authors.forename: Robert T
authors.initials: RT
authors.lastname: Huckstepp
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Dell
authors.forename: Baljit S
authors.initials: BS
authors.lastname: Khakh
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D056654:CA3 Region, Hippocampal / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000172:deficiency; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D018408:Patch-Clamp Techniques; D011687:Purines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012694:Serine / Q000378:metabolism*; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D005904:Glial Fibrillary Acidic Protein; D018841:HSP90 Heat-Shock Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047908:Intracellular Signaling Peptides and Proteins; C580990:Ip3r2 protein, mouse; D011687:Purines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C547760:TRAP-1 protein, mouse; D015091:beta-Alanine; D012694:Serine; D005680:gamma-Aminobutyric Acid; D002118:Calcium