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Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity

Tigaret, Cezar M. ORCID:, Olivo, Valeria, Sadowski, Josef H. L. P., Ashby, Michael C. and Mellor, Jack R. 2016. Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity. Nature Communications 7 (1) , 10289. 10.1038/ncomms10289

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At glutamatergic synapses, induction of associative synaptic plasticity requires time-correlated presynaptic and postsynaptic spikes to activate postsynaptic NMDA receptors (NMDARs). The magnitudes of the ensuing Ca2+ transients within dendritic spines are thought to determine the amplitude and direction of synaptic change. In contrast, we show that at mature hippocampal Schaffer collateral synapses the magnitudes of Ca2+ transients during plasticity induction do not match this rule. Indeed, LTP induced by time-correlated pre- and postsynaptic spikes instead requires the sequential activation of NMDARs followed by voltage-sensitive Ca2+ channels within dendritic spines. Furthermore, LTP requires inhibition of SK channels by mGluR1, which removes a negative feedback loop that constitutively regulates NMDARs. Therefore, rather than being controlled simply by the magnitude of the postsynaptic calcium rise, LTP induction requires the coordinated activation of distinct sources of Ca2+ and mGluR1-dependent facilitation of NMDAR function.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License.
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 14 January 2020
Date of Acceptance: 26 November 2015
Last Modified: 06 May 2023 04:07

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