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Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity.


ABSTRACT: Adenosine is a potent anticonvulsant acting on excitatory synapses through A1 receptors. Cellular release of ATP, and its subsequent extracellular enzymatic degradation to adenosine, could provide a powerful mechanism for astrocytes to control the activity of neural networks during high-intensity activity. Despite adenosine's importance, the cellular source of adenosine remains unclear. We report here that multiple enzymes degrade extracellular ATP in brain tissue, whereas only Nt5e degrades AMP to adenosine. However, endogenous A1 receptor activation during cortical seizures in vivo or heterosynaptic depression in situ is independent of Nt5e activity, and activation of astrocytic ATP release via Ca(2+) photolysis does not trigger synaptic depression. In contrast, selective activation of postsynaptic CA1 neurons leads to release of adenosine and synaptic depression. This study shows that adenosine-mediated synaptic depression is not a consequence of astrocytic ATP release, but is instead an autonomic feedback mechanism that suppresses excitatory transmission during prolonged activity.

SUBMITTER: Lovatt D 

PROVIDER: S-EPMC3341061 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity.

Lovatt Ditte D   Xu Qiwu Q   Liu Wei W   Takano Takahiro T   Smith Nathan A NA   Schnermann Jurgen J   Tieu Kim K   Nedergaard Maiken M  

Proceedings of the National Academy of Sciences of the United States of America 20120315 16


Adenosine is a potent anticonvulsant acting on excitatory synapses through A1 receptors. Cellular release of ATP, and its subsequent extracellular enzymatic degradation to adenosine, could provide a powerful mechanism for astrocytes to control the activity of neural networks during high-intensity activity. Despite adenosine's importance, the cellular source of adenosine remains unclear. We report here that multiple enzymes degrade extracellular ATP in brain tissue, whereas only Nt5e degrades AMP  ...[more]

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