ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression.
Extracellular ATP released from axons is known to assist activity-dependent signaling between neurons and Schwann cells in the peripheral nervous system. Here we report that ATP released from astrocytes as a result of neuronal activity can also modulate central synaptic transmission. In cultures of hippocampal neurons, endogenously released ATP tonically suppresses glutamatergic synapses via presynaptic P2Y receptors, an effect that depends on the presence of cocultured astrocytes. Glutamate release accompanying neuronal activity also activates non-NMDA receptors of nearby astrocytes and triggers ATP release from these cells, which in turn causes homo- and heterosynaptic suppression. In CA1 pyramidal neurons of hippocampal slices, a similar synaptic suppression was also produced by adenosine, an immediate degradation product of ATP released by glial cells. Thus, neuron-glia crosstalk may participate in activity-dependent synaptic modulation.
Zhang
Jing-ming
JM
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
Wang
Hui-kun
HK
Ye
Chang-quan
CQ
Ge
Wooping
W
Chen
Yiren
Y
Jiang
Zheng-lin
ZL
Wu
Chien-ping
CP
Poo
Mu-ming
MM
Duan
Shumin
S
D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D018698:Glutamic Acid; D000255:Adenosine Triphosphate