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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Manipulating the cytoskeleton of dendritic spines with light


To understand how the spine cytoskeleton feeds back onto postsynaptic scaffolds and synaptic function. To implement a new optogenetic tool in neurones. To set up correlative experiments involving optical microscopy / electron microscopy (with novel, genetically encoded markers) / electrophysiology.


Dendritic spines are tiny mushroom-shaped protrusions that form the receiving (post-synaptic) part of most excitatory synapses in the brain. Synaptic strengthening, a core mechanism of memory, correlates with an increase in spine size driven by a surge in actin filament formation. This latter is required to stabilise the enlarged spine, and becomes dysregulated in neurodegenerative diseases such as Alzheimer's. The mechanism responsible for stabilising the spine remains obscrue. We will explore the specific effects of cytoskeleton enlargement by using a novel optogenetic tool that allows direct activation of actin assembly upon illumination with blue light. Neurones will be made to express the optogenetic construct together with protein markers of the cytoskeleton or the postsynaptic density. The effects of actin polymerisation on spine morphology, composition and function will be studied by correlative light and electron microscopy, and (time permitting, collaboration with team Buisson), by electrophysiology.


Primary culture of hippocampal neurones; lentiviral vector construction; plasmid transfection; live cell confocal microscopy, photoactivation and uncaging; image analysis; statistics; cell staining; transmission electron microscopy; (possible) patch clamp.


  • Chassefeyre, R., Martinez-Hernandez, J., Bertaso, F., Bouquier, N., Blot, B., Laporte, M., Fraboulet, S., Coute, Y., Devoy, A., Isaacs, A.M., Pernet-Gallay, K., Sadoul, R., Fagni, L., Goldberg, Y. (2015). Regulation of postsynaptic function by the dementia-related ESCRT-III subunit CHMP2B. J. Neurosci. 35, 3155–3173.


Yves Goldberg, DR CEA
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Mise à jour le 23 mai 2017


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