Neuron Modeling

Neuron Modeling

Creation of a 3D Neuron Model

5a9b625bb0ede660ceab9d33db140342?s=128

Bradley Monk

April 11, 2014
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  1. interfacing surface receptor diffusion with scaffold-protein clusters: synthesis and predictions

    of a multilayered synaptic-stability model Project Overview PNAS Manuscript
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  3. Neurons that fire together, wire together (at synapses)

  4. Neurons that fire together, wire together (at synapses)

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  6. Scaffold Associated Proteins (SAP)

  7. Molecular Cell Biology

  8. It is generally accepted that memory formation involves receptor-mediated synaptic

    potentiation. Yet, a major question remains: how do synapses regulate potentiation despite perpetual turnover of their constituent parts? A number of theoretical models have been proposed to address this issue; to extend this work we developed a multilayer simulation environment that integrates several prior models into a unified framework. This multiplex model can simulate dendritic surface-receptor diffusion, postsynaptic scaffold protein clustering, and their dynamic interactions (with model parameters directly based on experimental data-points). We find that surface-receptors can enhance scaffold cluster stability through stochastic interactions, preventing cluster disintegration, and allowing clusters to persist for decades. Furthermore, transient changes in receptor-scaffold protein interaction properties can yield metastable cluster growth or shrinkage, leading to long- term potentiation or depression. Overall, the multiplex design of this model provides a novel framework for developing testable predictions about the nature of synaptic potentiation mechanics dynamics.
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  11. ¨  Model Synthesis

  12. ¨  Cluster Stabilization & Synaptic Depression

  13. ¨  Cluster Growth & Synaptic Potentiation

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  18. Hose Choquet Holcman 2012 Ehlers Choquet 2007

  19. Elias Nicoll 2007b Opazo Choquet 2012

  20. Scaffold Protein Clusters

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  36. Xu Sabatini Malenka 2008 ¨  10 min: 82% ¨  30

    min: 78% ¨  45 min: 66% ¨  60 min: 64% ¨  60 min low: ¤  62%
  37. Xu Sabatini Malenka 2008 N(t) = N 0 e−λt →

    N(t) = N 0 e−t/τ
  38. Xu Sabatini Malenka 2008 N(t) = N 0 e−λt →

    N(t) = N 0 e−t/τ
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  47. Bon Lon

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  50. Bon Lon Lon : 2 Bon : 10

  51. Ron Bon Ron : 15 Bon : 10

  52. Ron Bon

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  54. Ron Bon

  55. Ron Bon

  56. Bon Roff

  57. Bon Roff

  58. Cluster Lifetimes > 1 year Cluster Lifetimes > 10 years

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  60. ¨  10 min: 82% ¨  30 min: 78% ¨  45

    min: 66% ¨  60 min: 64% ¨  60 min low: ¤  62%
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  62. Work with Dan (“Berkeley Guy”)

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