Launey Resarch Unit

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 synapse between granule neurons and Purkinje neurons. Our aim is to fully characterize the molecular signaling cascades accompanying plasticity induction and the stable reorganization of protein assemblies and cellular organelles that underlies the formation of life-long memories. To achieve this goal, we synergistically study four aspects of signaling dynamics:

1. RNAs: By capturing the protein-coding RNAs specifically from Purkinje neurons, we want to establish an exhaustive "parts list" of all the proteins relevant to the function of this neuron.
2. Proteins: With Purkinje cell targeted neuroproteomics, we want to identify proteins newly synthesized in response to neuronal stimulation, with particular interest for proteins locally synthesized in dendrites.
3. Shape: With high-resolution 3D reconstruction of dendrite/spine ultrastructure, we want to characterize alterations of organelles following stimulation.
4. Interactions: With patch-clamp recording and fluorescence imaging of Purkinje cells in cerebellar circuit reconstituted in-vitro, we want to measure change of synaptic plasticity following ablation/alteration of specific proteins.

Ultimately, our aim is to construct a complete and accurate mechanistic description of all the molecular/cellular events within the spines and dendritic shaft of Purkinje cells, accounting for all forms of post-synaptic plasticity at synapses between granule and Purkinje neurons.

Research Subjects

• Neuron-type specific transcriptomics with sub-cellular resolution
• Proteomic-based identification of nascent proteins in Purkinje cell dendrites
• Activity-dependent change of dendritic organelle's shape and distribution
• Regulation of Purkinje cell plasticity by calcium channel-binding proteins

Publications

1. 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.
2. 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
3. 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.
4. 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
5. Perron A, Mutoh H, Launey T, Knöpfel T.:
   "Red-shifted voltage-sensitive fluorescent proteins."
   Chem Biol. 2009 Dec 24;16(12):1268-77.
6. 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.
7. 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
8. 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
9. 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
10. 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