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Kei Cho (Professor of Neuroscience) Henry Wellcome LINE and MRC Centre for Synaptic Plasticity

Medical Research Council. MRC. Centre for Synaptic Plasticity. Synaptic Plasticity: Pathways towards and away from Amyloid- b peptide-mediated synaptic dysfunction. Kei Cho (Professor of Neuroscience) Henry Wellcome LINE and MRC Centre for Synaptic Plasticity.

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Kei Cho (Professor of Neuroscience) Henry Wellcome LINE and MRC Centre for Synaptic Plasticity

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  1. Medical Research Council MRC Centre for Synaptic Plasticity Synaptic Plasticity: Pathways towards and away from Amyloid-b peptide-mediated synaptic dysfunction Kei Cho (Professor of Neuroscience) Henry Wellcome LINE and MRC Centre for Synaptic Plasticity How does Aβ influence synaptic plasticity? How does Aβ regulate postsynaptic proteins?

  2. Synaptic Transmission Cerebral elevation and accumulation of Ab1-42 peptide in many aspects of AD mediated pathogenesis. Oligomeric forms of Ab1-42in the extracellular space correlates with cognitive decline and synaptic alterations (impairment of LTP, inflammation, fibrillization) Synaptic Plasticity and Alzheimer’s Disease

  3. LTP LTD Ab The role of Ab in synaptic plasticity

  4. ?   Using a combination of biochemistry, molecular biology and electrophysiology, the project will explore whether soluble Ab regulates enzymes and postsynaptic protein-protein interactions involved in LTP and LTD.  Molecules of interest include PSD-95, GRIP1, PICK1, AMPARs, caspase and neuronal calcium sensors.    Target and Strategy Ab oligomers Signal cascades Plasma Membrane Output ? Extracellular Neurotoxicity, Cell death, Atrophy, Synaptic dysfunction Intracellular

  5. Approach 1 Electrophysiology: LTP/LTD, Basal synaptic transmission (AMPAR and NMDAR-mediated Synaptic current) Target Protein RNAi Fluorescence Marker Two-Photon image: Dendritic spine morphology, Spine / Presynaptic bouton calcium imaging, Time-lapse imaging Approach 2 Ab oligomers Protein Assay Brain slice culture with Ab Target Assays Method & Application Synaptic Transmission Synaptic Plasticity (LTP/LTD) Morphological Plasticity (multi-photon imaging) Protein-protein interaction (Co-IP/GST-Pull down/Western-blot) Dominant-negative shRNAi Interfering-peptide Overexpression Antibody Pharmacology

  6. Recent Relevant Publications from the Cho and Collingridge Groups LTP inhibits LTD in the hippocampus via regulation of GSK3beta (2007, Neuron 53, 703-717)  Synaptic accumulation of PSD-95 and synaptic function regulated by phosphorylation of serine-295 of PSD-95 (2007, Neuron 56, 488-502)  An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity (2008, Neuron, 57, 872-882)  Metabotropic glutamate receptor-mediated LTD involves two interacting Ca2+ sensors, NCS-1 and PICK1 (2008, Neuron, 60, 1095-1111) Postsynaptic neuron

  7. Molecule to Cognition Unit Satellite Research Facility Molecule to Cognition Unit Consortium: Graham Collingridge, Bong-Kiun Kaang, Sang-Jeong Kim and Min Zhou, Kei Cho (Adjunct Faculty)

  8. Brain & Cognitive Sciences, SNU, Korea Molecule to Cognition Unit United Kingdom Canada SPINE (Synaptic Plasticity & Integrative Neuroscience and Endocrinology), Bristol Physiology, Univ. of Toronto  MRC Centre for Synaptic Plasticity, Univ. of Bristol Henry Wellcome Laboratories for Integrative Neuroscience & Endocrinology, Univ. of Bristol

  9. SPINE, Bristol MRC Centre for Synaptic Plasticity (23PIs) Henry Wellcome LINE Alzheimer’s Disease Synaptic Plasticity & Repair Molecular Biology & Stem Cell Biology Stress & Endocrinology

  10. Multi-Photon Imaging Technique 1 mm Single-Photon Multi-Photon High resolution multi-photon image: dendrite with spines Multi-photon microscopy enables high resolution imaging in brain tissue (e.g. slices and in vivo). Confocal microscopy is limited to thin tissue preparations (cell cultures or organotypic slices)

  11. Not Just Experiment but also……..

  12. ‘Best Regards’ to All of You from Kei’s Lab Plus Me! Molecule to Cognition Unit Satellite Research Facility

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