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ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex
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Lalo, Ulyana, Palygin, Oleg, Verkhratsky, A., Grant, S. G. N. and Pankratov, Yuriy (2016) ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex. Scientific Reports, 6 . 33609. doi:10.1038/srep33609 ISSN 2045-2322.
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Official URL: http://dx.doi.org/10.1038/srep33609
Abstract
Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca2+-dependent mechanism. P2X receptors, co-localized with NMDA receptors in the excitatory synapses, can be activated by ATP co-released with glutamate from pre-synaptic terminals and by glia-derived ATP. An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca2+-dependent de-phosphorylation and interaction with PSD-95 multi-protein complex. Genetic deletion of the PSD-95 or P2X4 receptors obliterated ATP-mediated down-regulation of NMDA receptors. Impairment of purinergic modulation of NMDA receptors in the PSD-95 mutants dramatically decreased the threshold of LTP induction and increased the net magnitude of LTP. Our findings show that synergistic action of glia- and neurone-derived ATP can pre-modulate efficacy of excitatory synapses and thereby can have an important role in the glia-neuron communications and brain meta-plasticity.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Neurons, Synapses, Astrocytes, Neuroglia | ||||||||
Journal or Publication Title: | Scientific Reports | ||||||||
Publisher: | Nature Publishing Group | ||||||||
ISSN: | 2045-2322 | ||||||||
Official Date: | 19 September 2016 | ||||||||
Dates: |
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Volume: | 6 | ||||||||
Article Number: | 33609 | ||||||||
DOI: | 10.1038/srep33609 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 22 September 2016 | ||||||||
Date of first compliant Open Access: | 22 September 2016 | ||||||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) | ||||||||
Grant number: | Grant BB/ K009192/1 | ||||||||
Adapted As: |
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