Abstract
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.
MeSH Terms
Adenosine/metabolism
Adenosine A1 Receptor Antagonists
Adenosine Triphosphatases/antagonists & inhibitors
Adenosine Triphosphate/analogs & derivatives,metabolism,pharmacology
Animals
Astrocytes/drug effects,physiology
Cells, Cultured
Excitatory Postsynaptic Potentials
Hippocampus/drug effects,physiology
In Vitro Techniques
Long-Term Potentiation/drug effects
Mice
Mice, Transgenic
Neuronal Plasticity/drug effects
Purinergic P1 Receptor Antagonists
Purinergic P2 Receptor Antagonists
Receptor, Adenosine A1/metabolism
Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors,metabolism
Receptors, Purinergic P1/metabolism
Receptors, Purinergic P2/metabolism
Synapses/physiology
Synaptic Transmission/drug effects
Xanthines/pharmacology
Chemicals
6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP
Adenosine A1 Receptor Antagonists
NR2B NMDA receptor
Purinergic P1 Receptor Antagonists
Purinergic P2 Receptor Antagonists
Receptor, Adenosine A1
Receptors, N-Methyl-D-Aspartate
Receptors, Purinergic P1
Receptors, Purinergic P2
Xanthines
Adenosine Triphosphate
1,3-dipropyl-8-cyclopentylxanthine
Adenosine Triphosphatases
Adenosine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pascual Olivier
Department of Neuroscience, Conte Center for Integration at the Tripartite Synapse, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Casper Kristen B
Kubera Cathryn
Zhang Jing
Revilla-Sanchez Raquel
Sul Jai-Yoon
Takano Hajime
Moss Stephen J
McCarthy Ken
Haydon Philip G