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Thesis defense – Sandra Dubes

Monday 24 June 2019 / 14:30

miR-124 is required for synaptic scaling induction by controlling the expression of synaptopodin and AMPA receptors in hippocampal neurons, miR-124 is required for synaptic scaling induction by controlling the expression of synaptopodin and AMPA receptors in hippocampal neurons

Venue : Neurocentre Magendie conference room

Sandra Dubes
Thesis supervisor : Mathieu Letellier ; team “Cell adhesion molecules in synapse assembly

Abstract

Synaptic scaling is a form of homeostatic plasticity where synapses adjust their own efficacy to compensate for normal or pathological variations in neuronal activity such as neurodegenerative disorders or sensory deprivation after a lesion. In a well-established paradigm, the chronic application of tetrodotoxin (TTX) in primary neurons, to block presynaptic action potential propagation, induces a significant upscaling of miniature excitatory postsynaptic currents mediated-AMPA receptors. Numerous regulators of this plasticity have been identified including microRNAs (miRs), which are small endogenous non-coding RNAs, inhibiting protein translation by binding to mRNA targets. This led us to hypothesize that the most highly expressed microRNA in the brain, miR-124, could be an important regulator of homeostatic scaling by controlling the expression of synaptopodin, a structural protein of dendritic spines playing a crucial role in homeostatic plasticity.

By combining qRT-PCR, immunocytochemistry and in vitro electrophysiology approaches, first we showed that a global 48 hrs TTX treatment in hippocampal primary neurons led to a decrease in miR-124 level and an increase in the expression of synaptopodin and synaptic AMPA receptors containing the GluA2 subunit which is another miR-124 target. Moreover, we observed that the synaptic accumulation of AMPA receptors and synaptopodin could be synapse-specific by expressing the tetanus toxin to block the activity of individual presynapses, which suggested a local homeostatic regulation. Importantly, we found that overexpressing miR-124 or inhibiting its interaction with synaptopodin or GluA2 mRNAs blocked the synaptic homeostatic response. In addition, FRAP experiments suggested that synaptopodin controlled AMPA receptor trafficking at the membrane by probably retaining them in dendritic spines, which could explain its role during homeostatic plasticity.

Key words : homeostatic plasticity, synaptic scaling, miR-124, synaptopodin, AMPA receptors

Jury

  • Nathalie Sans – Présidente du jury
  • Cyril Hanus – Rapporteur
  • Jean-Christophe Poncer – Rapporteur
  • Isabelle Caillé – Examinatrice
  • Mathieu Letellier – Directeur de thèse
  • Olivier Thoumine – Invité

Coming soon

  1. Monthly conference (PhD seminar series) – Laurent Bourdieu

    Friday 6 September 2019 / 11:30

    Fast 3D imaging of neuronal activity in visual cortex across multiple layers in awake mice

  2. Cajal lectures : Whole brain imaging

    Monday 9 September 2019 - Friday 27 September 2019

    Free entrance lectures / Venue: CGFB

  3. Seminar – Francesco Papaleo

    Friday 13 September 2019 / 11:30

    Bottom-Up and Top-Down Control of Emotion Recognition.

  4. LabEx TRAIL scientific day

    Monday 16 September 2019 / 14:00 - 18:00

    Dedicated to brain connectivity.

  5. Synapse Day

    Tuesday 17 September 2019

    Centre Broca Nouvelle-Aquitaine


Conférence internationale : REWARD

Du 2 au 4 octobre

L’événement en un coup d’oeil :
télécharger le livret (programme,
inscription, soumission d’abstract…)

brainconf.u-bordeaux.fr

Details

Date:
Monday 24 June 2019
Time:
14:30
Event Category: