Bidirectional astrocyte-neuron communication: the many roles of glutamate and ATP.
Glutamatergic and purinergic signalling play key roles in synaptic transmission and modulation in the CNS. Here, we review recent evidence showing that glial cells, and in particular astrocytes, are active players in ATP and glutamate signalling in the brain. ATP and glutamate coordinately activate astrocytes, through the mobilization of their internal Ca2+, which in turn triggers the release from astrocytes of several neuroactive molecules including ATP and glutamate themselves. These 'gliotransmitters' signal either to astrocytes, where they generate Ca2+ waves, or to neurons, where they modulate synaptic transmission and neuronal excitability. By using microfabricated lanes of adhesive substrate, we provide further evidence for a diffusible factor-mediated propagation of Ca2+ waves and, through flash photolysis experiments in hippocampal slices, we show that glutamate and ATP cooperate in the generation of the astrocytic Ca2+ signal. Once astrocytes are activated they provide both excitatory and inhibitory effects on neighbouring neurons. Through the Ca2+-dependent release of glutamate, which acts on extrasynaptic neuronal NMDA receptors, astrocytes excite neurons while, in contrast, ATP released from astrocytes, after the delayed conversion to adenosine, causes neuronal suppression.
Fellin
Tommaso
T
Silvio Conte Center for Integration at the Tripartite Synapse, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Sul
Jai-Yoon
JY
D'Ascenzo
Marcello
M
Takano
Hajime
H
Pascual
Olivier
O
Haydon
Philip G
PG
D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002450:Cell Communication; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium