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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Neuronal activity and the regulation of intra-axonal dynamics and synapse function

Objectifs

The objectives of the project are to understand how neuronal activity regulates intra-axonal dynamics and synapse function using microfluidics systems connected to multielectrode arrays.

Résumé

Dynamic remodeling of axonal connections in the adult brain is a prerequisite for behavioral adaptation to environmental changes. BDNF, the most abundant neurotrophin in the adult brain plays a central role in axonal remodeling that conditions complex cognitive function and long-term memory. But how is BDNF transport in axons regulated and how is it selectively targeted to activated synapses?
Using microfluidics reconstruction of neuronal networks, multielectrode arrays, super-resolution videomicroscopy and computational modeling, we want to investigate modes of transport and decipher the signaling pathways as well as the energy sources allowing neurons to adapt to high neuronal demands during long-term memory. The goal of this project is to use this model to identify the molecular and cellular events that decode neuronal activity into BDNF transport to the active synapse in health and disease such as Huntington’s disease.

Méthodes

Techniques used will include molecular biology, biochemistry, primary cultures, state of the art live-imaging microscopy and the development and use of new microfluidic devices coupled to micro-electrode arrays to study intracellular dynamics in connected neuronal networks.

Références

  • Hinckelmann MV, et al., (2016) Self-propelling vesicles define glycolysis as the minimal energy machinery for neuronal transport Nature Communications, 7:13233. doi: 10.1038/ncomms13233.
  • El-Daher MT et al. (2015) Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation. EMBO J. 34(17):2255-71. doi: 10.15252/embj.201490808.
  • Zala D, et al. (2013) Vesicular glycolysis provides on-board energy for axonal transport. Cell. 152, 479-91. doi: 10.1016/j.cell.2012.12.029.

Contacts

Frédéric Saudou, PU-PH1 UGA, & Maxime Cazorla, CR1 Inserm
Email : frederic.saudou@univ-grenoble-alpes.fr

Mise à jour le 23 mai 2017

Contacts

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Pour les stages de licence et de 3ème, utilisez les formulaires de demande spécifiques : stage de 3ème ou stage de licence UGA. 

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