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Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus

Tigaret, Cezar M., Chamberlain, Sophie E. L., Sadowski, Joseph H. L. P., Hall, Jeremy, Ashby, Michael C. and Mellor, Jack R. 2018. Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus. Journal of Neuroscience 38 (43) , pp. 9252-9262. 10.1523/JNEUROSCI.1160-18.2018

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Abstract

Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place cell firing patterns that occur in sharp wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place cell firing patterns during exploration. Thus, we describe a common mechanism that enables synaptic plasticity during both encoding and consolidation of memories within hippocampal circuits.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 12 October 2018
Date of Acceptance: 9 August 2018
Last Modified: 29 Apr 2019 10:32
URI: http://orca.cf.ac.uk/id/eprint/115820

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