TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus.
Details
Serval ID
serval:BIB_9FE8ED280ECC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus.
Journal
Neuron
ISSN
1097-4199 (Electronic)
ISSN-L
0896-6273
Publication state
Published
Issued date
2011
Volume
69
Number
5
Pages
988-1001
Language
english
Abstract
Glutamatergic gliotransmission provides a stimulatory input to excitatory synapses in the hippocampal dentate gyrus. Here, we show that tumor necrosis factor-alpha (TNFα) critically controls this process. With constitutive TNFα present, activation of astrocyte P2Y1 receptors induces localized [Ca(2+)](i) elevations followed by glutamate release and presynaptic NMDA receptor-dependent synaptic potentiation. In preparations lacking TNFα, astrocytes respond with identical [Ca(2+)](i) elevations but fail to induce neuromodulation. We find that TNFα specifically controls the glutamate release step of gliotransmission. In cultured astrocytes lacking TNFα glutamate exocytosis is dramatically slowed down due to altered vesicle docking. Addition of low picomolar TNFα promptly reconstitutes both normal exocytosis in culture and gliotransmission in situ. Alternatively, gliotransmission can be re-established without adding TNFα, by limiting glutamate uptake, which compensates slower release. These findings demonstrate that gliotransmission and its synaptic effects are controlled not only by astrocyte [Ca(2+)](i) elevations but also by permissive/homeostatic factors like TNFα. VIDEO ABSTRACT:
Keywords
Animals, Astrocytes/cytology, Astrocytes/metabolism, Calcium/metabolism, Cell Communication/physiology, Cells, Cultured, Dentate Gyrus/metabolism, Electrophysiology, Excitatory Postsynaptic Potentials/physiology, Exocytosis/physiology, Glutamic Acid/metabolism, Mice, Mice, Transgenic, Miniature Postsynaptic Potentials/physiology, Receptors, Purinergic P2Y1/metabolism, Synapses/metabolism, Synaptic Vesicles/metabolism, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
18/04/2011 15:20
Last modification date
20/08/2019 15:06