miR ‐124‐dependent tagging of synapses by synaptopodin enables input‐specific homeostatic plasticity

Abstract: Homeostatic synaptic plasticity is a process by which neurons adjust their synaptic strength to compensate for perturbations in neuronal activity. Whether the highly diverse synapses on a neuron respond uniformly to the same perturbation remains unclear. Moreover, the molecular determinants that underlie synapse‐specific homeostatic synaptic plasticity are unknown. Here, we report a synaptic tagging mechanism in which the ability of individual synapses to increase their strength in response to activity deprivation depends on the local expression of the spine‐apparatus protein synaptopodin under the regulation of miR‐124. Using genetic manipulations to alter synaptopodin expression or regulation by miR‐124, we show that synaptopodin behaves as a “postsynaptic tag” whose translation is derepressed in a subpopulation of synapses and allows for nonuniform homeostatic strengthening and synaptic AMPA receptor stabilization. By genetically silencing individual connections in pairs of neurons, we demonstrate that this process operates in an input‐specific manner. Overall, our study shifts the current view that homeostatic synaptic plasticity affects all synapses uniformly to a more complex paradigm where the ability of individual synapses to undergo homeostatic changes depends on their own functional and biochemical state.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
miR ‐124‐dependent tagging of synapses by synaptopodin enables input‐specific homeostatic plasticity ; day:25 ; month:07 ; year:2022 ; extent:31
The EMBO journal / European Molecular Biology Organization ; (25.07.2022) (gesamt 31)

Urheber
Dubes, Sandra
Soula, Anaïs
Benquet, Sébastien
Tessier, Béatrice
Poujol, Christel
Favereaux, Alexandre
Thoumine, Olivier
Letellier, Mathieu

DOI
10.15252/embj.2021109012
URN
urn:nbn:de:101:1-2022072515175802946623
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:21 MESZ

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Beteiligte

  • Dubes, Sandra
  • Soula, Anaïs
  • Benquet, Sébastien
  • Tessier, Béatrice
  • Poujol, Christel
  • Favereaux, Alexandre
  • Thoumine, Olivier
  • Letellier, Mathieu

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