CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment

© 2019 The Authors A key feature of brain plasticity is the experience-dependent selection of optimal connections, implemented by a set of activity-regulated genes that dynamically adjust synapse strength and number. The activity-regulated gene cpg15/neuritin has been previously implicated in stabil...

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Main Authors: Subramanian, Jaichandar, Michel, Katrin, Benoit, Marc, Nedivi, Elly
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/136399
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author Subramanian, Jaichandar
Michel, Katrin
Benoit, Marc
Nedivi, Elly
author_facet Subramanian, Jaichandar
Michel, Katrin
Benoit, Marc
Nedivi, Elly
author_sort Subramanian, Jaichandar
collection MIT
description © 2019 The Authors A key feature of brain plasticity is the experience-dependent selection of optimal connections, implemented by a set of activity-regulated genes that dynamically adjust synapse strength and number. The activity-regulated gene cpg15/neuritin has been previously implicated in stabilization and maturation of excitatory synapses. Here, we combine two-photon microscopy with genetic and sensory manipulations to dissect excitatory synapse formation in vivo and examine the role of activity and CPG15 in dendritic spine formation, PSD95 recruitment, and synapse stabilization. We find that neither visual experience nor CPG15 is required for spine formation. However, PSD95 recruitment to nascent spines and their subsequent stabilization requires both. Further, cell-autonomous CPG15 expression is sufficient to replace experience in facilitating PSD95 recruitment and spine stabilization. CPG15 directly interacts with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on immature dendritic spines, suggesting a signaling mode for this small extracellular molecule acting as an experience-dependent “selector” for spine stabilization and synapse maturation. Experience plays a key role in formation and continuous optimization of brain circuits. Subramanian et al. show that the molecule CPG15/neuritin can replace experience in selecting which nascent contacts between neurons are retained, facilitating the recruitment of proteins that promote synapse maturation and stabilization.
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spelling mit-1721.1/1363992021-10-28T03:16:28Z CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment Subramanian, Jaichandar Michel, Katrin Benoit, Marc Nedivi, Elly © 2019 The Authors A key feature of brain plasticity is the experience-dependent selection of optimal connections, implemented by a set of activity-regulated genes that dynamically adjust synapse strength and number. The activity-regulated gene cpg15/neuritin has been previously implicated in stabilization and maturation of excitatory synapses. Here, we combine two-photon microscopy with genetic and sensory manipulations to dissect excitatory synapse formation in vivo and examine the role of activity and CPG15 in dendritic spine formation, PSD95 recruitment, and synapse stabilization. We find that neither visual experience nor CPG15 is required for spine formation. However, PSD95 recruitment to nascent spines and their subsequent stabilization requires both. Further, cell-autonomous CPG15 expression is sufficient to replace experience in facilitating PSD95 recruitment and spine stabilization. CPG15 directly interacts with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on immature dendritic spines, suggesting a signaling mode for this small extracellular molecule acting as an experience-dependent “selector” for spine stabilization and synapse maturation. Experience plays a key role in formation and continuous optimization of brain circuits. Subramanian et al. show that the molecule CPG15/neuritin can replace experience in selecting which nascent contacts between neurons are retained, facilitating the recruitment of proteins that promote synapse maturation and stabilization. 2021-10-27T20:35:11Z 2021-10-27T20:35:11Z 2019 2019-10-03T16:09:56Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136399 en 10.1016/j.celrep.2019.07.012 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier
spellingShingle Subramanian, Jaichandar
Michel, Katrin
Benoit, Marc
Nedivi, Elly
CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment
title CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment
title_full CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment
title_fullStr CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment
title_full_unstemmed CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment
title_short CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment
title_sort cpg15 neuritin mimics experience in selecting excitatory synapses for stabilization by facilitating psd95 recruitment
url https://hdl.handle.net/1721.1/136399
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