Astrocytic purinergic signaling coordinates synaptic networks.
To investigate the role of astrocytes in regulating synaptic transmission, we generated inducible transgenic mice that express a dominant-negative SNARE domain selectively in astrocytes to block the release of transmitters from these glial cells. By releasing adenosine triphosphate, which accumulates as adenosine, astrocytes tonically suppressed synaptic transmission, thereby enhancing the dynamic range for long-term potentiation and mediated activity-dependent, heterosynaptic depression. These results indicate that astrocytes are intricately linked in the regulation of synaptic strength and plasticity and provide a pathway for synaptic cross-talk.
Pascual
Olivier
O
Department of Neuroscience, Conte Center for Integration at the Tripartite Synapse, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Casper
Kristen B
KB
Kubera
Cathryn
C
Zhang
Jing
J
Revilla-Sanchez
Raquel
R
Sul
Jai-Yoon
JY
Takano
Hajime
H
Moss
Stephen J
SJ
McCarthy
Ken
K
Haydon
Philip G
PG
D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D058916:Adenosine A1 Receptor Antagonists; C121001:NR2B NMDA receptor; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D043682:Receptor, Adenosine A1; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014970:Xanthines; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000251:Adenosine Triphosphatases; D000241:Adenosine