Rewiring neuronal microcircuits of the brain via spine head protrusions--a role for synaptopodin and intracellular calcium stores.

Détails

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Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_A1C9805FEE66
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Rewiring neuronal microcircuits of the brain via spine head protrusions--a role for synaptopodin and intracellular calcium stores.
Périodique
Acta Neuropathologica Communications
Auteur⸱e⸱s
Verbich D., Becker D., Vlachos A., Mundel P., Deller T., McKinney R.A.
ISSN
2051-5960 (Electronic)
ISSN-L
2051-5960
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
4
Pages
38
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Neurological diseases associated with neuronal death are also accompanied by axonal denervation of connected brain regions. In these areas, denervation leads to a decrease in afferent drive, which may in turn trigger active central nervous system (CNS) circuitry rearrangement. This rewiring process is important therapeutically, since it can partially recover functions and can be further enhanced using modern rehabilitation strategies. Nevertheless, the cellular mechanisms of brain rewiring are not fully understood. We recently reported a mechanism by which neurons remodel their local connectivity under conditions of network-perturbance: hippocampal pyramidal cells can extend spine head protrusions (SHPs), which reach out toward neighboring terminals and form new synapses. Since this form of activity-dependent rewiring is observed only on some spines, we investigated the required conditions. We speculated, that the actin-associated protein synaptopodin, which is involved in several synaptic plasticity mechanisms, could play a role in the formation and/or stabilization of SHPs. Using hippocampal slice cultures, we found that ~70 % of spines with protrusions in CA1 pyramidal neurons contained synaptopodin. Analysis of synaptopodin-deficient neurons revealed that synaptopodin is required for the stability but not the formation of SHPs. The effects of synaptopodin could be linked to its role in Ca(2+) homeostasis, since spines with protrusions often contained ryanodine receptors and synaptopodin. Furthermore, disrupting Ca(2+) signaling shortened protrusion lifetime. By transgenically reintroducing synaptopodin on a synaptopodin-deficient background, SHP stability could be rescued. Overall, we show that synaptopodin increases the stability of SHPs, and could potentially modulate the rewiring of microcircuitries by making synaptic reorganization more efficient.
Mots-clé
Animals, Animals, Newborn, Calcium/metabolism, Dendritic Spines/drug effects, Dendritic Spines/physiology, Endoplasmic Reticulum/metabolism, Enzyme Inhibitors/pharmacology, Female, Green Fluorescent Proteins/genetics, Green Fluorescent Proteins/metabolism, Hippocampus/cytology, Imaging, Three-Dimensional, In Vitro Techniques, Indoles/pharmacology, Intracellular Fluid/drug effects, Intracellular Fluid/metabolism, Male, Mice, Mice, Transgenic, Neurons/cytology, Neurons/drug effects, Sodium Channel Blockers/pharmacology, Synapses/metabolism, Synaptophysin/genetics, Synaptophysin/metabolism, Tetrodotoxin/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/05/2016 17:46
Dernière modification de la notice
20/08/2019 15:07
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