title: Heterosynaptic long-term depression mediated by ATP released from astrocytes.
abstract: Heterosynaptic long-term depression (hLTD) at untetanized synapses accompanying the induction of long-term potentiation (LTP) spatially sharpens the activity-induced synaptic potentiation; however, the underlying mechanism remains unclear. We found that hLTD in the hippocampal CA1 region is caused by stimulation-induced ATP release from astrocytes that suppresses transmitter release from untetanized synaptic terminals via activation of P2Y receptors. Selective stimulation of astrocytes expressing channelrhodopsin-2, a light-gated cation channel permeable to Ca(2+) , resulted in LTD of synapses on neighboring neurons. This synaptic modification required Ca(2+) elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors. Furthermore, blocking P2Y receptors or buffering astrocyte intracellular Ca(2+) at a low level prevented hLTD without affecting LTP induced by SC stimulation. Thus, astrocyte activation is both necessary and sufficient for mediating hLTD accompanying LTP induction, strongly supporting the notion that astrocytes actively participate in activity-dependent synaptic plasticity of neural circuits.
authors.affiliation: Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Chen
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Tan
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Zhang
authors.forename: You
authors.initials: Y
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wu
authors.forename: Yuju
authors.initials: Y
authors.lastname: Li
authors.forename: Bitao
authors.initials: B
authors.lastname: Bu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000737:chemistry* / Q000378:metabolism; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005822:Genetic Vectors / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D055620:Optical Phenomena; D018408:Patch-Clamp Techniques; D011509:Proteoglycans / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D012694:Serine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000241:Adenosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000941:Antigens; D002118:Calcium; D000075402:Channelrhodopsins; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D011509:Proteoglycans; D058915:Purinergic P1 Receptor Antagonists; D058921:Purinergic P2Y Receptor Antagonists; D012694:Serine; D013806:Theophylline; D000099216:Chondroitin Sulfate Proteoglycan 4; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C053907:8-cyclopentyl-1,3-dimethylxanthine