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Molecular control of spine dynamics in hippocampal organotypic cultures

English title Molecular control of spine dynamics in hippocampal organotypic cultures
Applicant Lüscher Christian
Number 144080
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2012 - 30.09.2016
Approved amount 1'022'829.00
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Keywords (2)

Plasticité synaptique; Synaptogenèse

Lay Summary (English)

Lead
Lay summary

Adaptation of synaptic networks during development and in response to learning behaviours occurs through a continuous process of synapse formation and elimination. At least two distinct mechanisms play a central role in these processes: one involves a selective stabilization of synapses through activity-dependent mechanisms and a second involves modifications of synapse turnover and dynamics to allow network rewiring. The molecular mechanisms underlying these two aspects of synaptic structural plasticity are still mainly unknown. Using organotypic slice cultures and a multidisciplinary approach involving imaging, morphological, molecular and electrophysiological techniques, our aim is to identify molecular pathways regulating structural plasticity of both excitatory and inhibitory synapses and examine their implication in cognitive dysfunctions.  

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles.
Stefanelli Thomas, Bertollini Cristina, Lüscher Christian, Muller Dominique, Mendez Pablo (2016), Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles., in Neuron, 89(5), 1074-85.
Activity-dependent inhibitory synapse remodeling through gephyrin phosphorylation.
Flores Carmen E, Nikonenko Irina, Mendez Pablo, Fritschy Jean-Marc, Tyagarajan Shiva K, Muller Dominique (2015), Activity-dependent inhibitory synapse remodeling through gephyrin phosphorylation., in Proceedings of the National Academy of Sciences of the United States of America, 112(1), 65-72.
Synthesis of FMRFaNV, a Photoreleasable Caged Transmitter Designed to Study Neuron-Glia Interactions in the Central Nervous System.
Janett Elia, Bernardinelli Yann, Müller Dominique, Bochet Christian G (2015), Synthesis of FMRFaNV, a Photoreleasable Caged Transmitter Designed to Study Neuron-Glia Interactions in the Central Nervous System., in Bioconjugate chemistry, 26(12), 2408-18.
Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability.
Bernardinelli Yann, Randall Jerome, Janett Elia, Nikonenko Irina, König Stéphane, Jones Emma Victoria, Flores Carmen E, Murai Keith K, Bochet Christian G, Holtmaat Anthony, Muller Dominique (2014), Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability., in Current biology : CB, 24(15), 1679-88.
GluN3A promotes dendritic spine pruning and destabilization during postnatal development.
Kehoe Laura A, Bellone Camilla, De Roo Mathias, Zandueta Aitor, Dey Partha Narayan, Pérez-Otaño Isabel, Muller Dominique (2014), GluN3A promotes dendritic spine pruning and destabilization during postnatal development., in The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(28), 9213-21.
Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome.
Boda Bernadett, Mendez Pablo, Boury-Jamot Benjamin, Magara Fulvio, Muller Dominique (2014), Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome., in The European journal of neuroscience, 39(7), 1130-7.
Nitric oxide mediates local activity-dependent excitatory synapse development.
Nikonenko Irina, Nikonenko Alexander, Mendez Pablo, Michurina Tatyana V, Enikolopov Grigori, Muller Dominique (2013), Nitric oxide mediates local activity-dependent excitatory synapse development., in Proceedings of the National Academy of Sciences of the United States of America, 110(44), E4142-E4151.
Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning.
Brown Matthew T C, Tan Kelly R, O'Connor Eoin C, Nikonenko Irina, Muller Dominique, Lüscher Christian (2012), Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning., in Nature, 492(7429), 452-6.

Collaboration

Group / person Country
Types of collaboration
JM Fritschy, Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
157747 High resolution 3D electron microscopy. A new tool for cell biology. 01.04.2015 R'EQUIP
127552 Molecular control of spine dynamics in hippocampal slice cultures 01.10.2009 Project funding (Div. I-III)

Abstract

Adaptation of synaptic networks during development and in response to learning behaviours occurs through a continuous process of synapse formation and elimination. At least two distinct mechanisms play a central role in these processes: one involves a selective stabilization of synapses through activity-dependent mechanisms and a second involves modifications of synapse turnover and dynamics to allow network rewiring. The molecular mechanisms underlying these two aspects of synaptic structural plasticity are still mainly unknown. The objectives of this project are to characterize the role of several candidate molecules for which we have preliminary evidence that they contribute to synapse turnover and stabilization during development. The work will focus on a model of organotypic slice cultures using repetitive imaging approaches, molecular tools and electrophysiological recordings to determine i) the specific function of nitric oxide in controlling clustered spine growth, ii) the role of the GluN3A subunit of NMDA receptors in spine elimination during development and iii) the alterations of spine dynamics present in a mouse model of Fragile X syndrome.
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