McLeod, F;
Boyle, K;
Marzo, A;
Martin-Flores, N;
Moe, TZ;
Palomer, E;
Gibb, AJ;
(2020)
Wnt Signaling Through Nitric Oxide Synthase Promotes the Formation of Multi-Innervated Spines.
Frontiers in Synaptic Neuroscience
, 12
, Article 575863. 10.3389/fnsyn.2020.575863.
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Abstract
Structural plasticity of synapses correlates with changes in synaptic strength. Dynamic modifications in dendritic spine number and size are crucial for long-term potentiation (LTP), the cellular correlate of learning and memory. Recent studies have suggested the generation of multi-innervated spines (MIS), in the form of several excitatory presynaptic inputs onto one spine, are crucial for hippocampal memory storage. However, little is known about the molecular mechanisms underlying MIS formation and their contribution to LTP. Using 3D enhanced resolution confocal images, we examined the contribution of Wnt synaptic modulators in MIS formation in the context of LTP. We show that blockage of endogenous Wnts with specific Wnt antagonists supresses the formation of MIS upon chemical LTP induction in cultured hippocampal neurons. Gain- and loss-of-function studies demonstrate that Wnt7a signaling promotes MIS formation through the postsynaptic Wnt scaffold protein Disheveled 1 (Dvl1) by stimulating neuronal nitric oxide (NO) synthase (nNOS). Subsequently, NO activates soluble guanylyl cyclase (sGC) to increase MIS formation. Consistently, we observed an enhanced frequency and amplitude of excitatory postsynaptic currents. Collectively, our findings identify a unique role for Wnt secreted proteins through nNOS/NO/sGC signaling to modulate MIS formation during LTP.
| Type: | Article |
|---|---|
| Title: | Wnt Signaling Through Nitric Oxide Synthase Promotes the Formation of Multi-Innervated Spines |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnsyn.2020.575863 |
| Publisher version: | https://doi.org/10.3389/fnsyn.2020.575863 |
| Language: | English |
| Additional information: | Copyright © 2020 McLeod, Boyle, Marzo, Martin-Flores, Moe, Palomer, Gibb and Salinas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | multi-innervated spines, structural plasticity, LTP, Wnt signaling, nitric oxide |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10111059 |
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