Launey Research Unit
Unit Leader
Thomas LAUNEY (Ph.D.)
Proteins are short-lived but the memories that they encode in the nervous tissue may last for decades. We are investigating the cellular and molecular basis of long term synaptic plasticity in the cerebellum, at the granule cell-Purkinje cell synapses. Our aim is to fully characterize the molecular signaling cascades accompanying plasticity induction and the stable reorganization of protein assemblies that underlies the formation of life-long stable engram in spite of molecular turnover. To achieve this goal, we synergistically study four aspects of signaling:
(1) Movements: With high-speed multispectral tracking of proteins movement to identify the factors controlling translocation dynamic in Purkinje cells in vitro;
(2) Components: With Purkinje cell targeted neuroproteomics and transcriptomics to clarify the role of newly synthesized proteins during plasticity in dendrites.
(3) Environments: with high-resolution 3D reconstruction of dendrite/spine ultrastructure to characterize morphological determinants of protein movement and clustering.
(4) Kinetic Measurement: with in silico construction of realistic 3D simulations of cellular signaling, based on experimentally validated parameters, to generate testable predictions of reaction and translocation dynamics.
Ultimately, we predict that this multidisciplinary integration will lead to construct a complete and accurate mechanistic description of molecular signaling within the spines and dendritic shaft of Purkinje cells, accounting for all forms of plasticity at these synapses.
- Multiplexed protein tracking of Qdot-labelled proteins injected into cultured Purkinje cells dendrites.
- sub-cellular transcriptomics of neuronal dendrites
- Proteomic-based identification of nascent proteins in Purkinje cell dendrites.
- Simulation of stochastic reaction-diffusion, in realistic 3D reconstruction of Purkinje cell dendrites.
- Sur S, Pashuck ET, Guler MO, Ito M, Stupp SI, Launey T.:
" A hybrid nanofiber matrix to control the survival and maturation of brain neurons."
Biomaterials. (2012) 33(2), 545-55. - Chimura T, Launey T, Ito M.:
" Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif"
BMC Genomics. (2011) 12:300, 1-12 - Launey T, Endo S, Sakai R, Harano J, and Ito M.:
" Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor."
Proc.Natl.Acad.Sci.U.S.A (2004) 101, 676-681. - Endo S, Launey T.:
" Nitric oxide activates extracellular signal-regulated kinase 1/2 and enhances declustering of ionotropic glutamate receptor subunit 2/3 in rat cerebellar Purkinje cells."
Neurosci. Lett. (2003) 350(2), 122-126 - Hirai H, Launey T, Mikawa S, Yanagihara D, Kasaura T, Miyamoto A, Yuzaki M.:
" Antibody against a putative ligand binding site reveals the d2 glutamate receptor function."
Nature Neuroscience (2003) 6(8), 869-876 - Matsuda S, Launey T, Mikawa S, and Hirai H.:
" Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons."
EMBO Journal (2000) 19 (2), 2765-2774 - Hirai H, and Launey T.:
" A regulatory connection between the activity of granule cell NMDA receptors and dendritic differentiation of cerebellar Purkinje cells."
Journal of Neurocience (2000) 20 (14), 5217-5224 - Bannai H, Lévi S, Schweizer C, Inoue T, Launey T, Racine V, Sibarita JB, Mikoshiba K, Triller A.:
" Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics."
Neuron. 2009 Jun 11;62(5):670-82 - Perron A, Mutoh H, Launey T, Knöpfel T.:
" Red-shifted voltage-sensitive fluorescent proteins."
Chem Biol. 2009 Dec 24;16(12):1268-77. - Iannella NL, Launey T, Tanaka S.:
" Spike timing-dependent plasticity as the origin of the formation of clustered synaptic efficacy engrams."
Front Comput Neurosci. 2010 Jul 14;4. pii: 21.
Principal Investigator
- Thomas LAUNEY
- Unit Leader
Members
- Pascal Yves BEGUIN
- Research Scientist
- Rejan VIGOT
- Research Scientist
- Yumiko MOTOYAMA
- Technical Staff I
- Atsuko MATSUNAGA
- Technical Staff II
- Charles ROCKLAND
- Visiting Scientist
- Takahiko CHIMURA
- Visiting Scientist
- Nicolangelo IANNELLA
- Visiting Scientist