Neuron Modeling

Creation of a 3D Neuron Model

Transcript

1. interfacing surface receptor diffusion with scaffold-protein clusters: synthesis and predictions of a multilayered synaptic-stability model Project Overview PNAS Manuscript
3. Neurons that fire together, wire together (at synapses)
4. Neurons that fire together, wire together (at synapses)
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.
11. ¨  Model Synthesis
12. ¨  Cluster Stabilization & Synaptic Depression
13. ¨  Cluster Growth & Synaptic Potentiation
18. Hose Choquet Holcman 2012 Ehlers Choquet 2007
19. Elias Nicoll 2007b Opazo Choquet 2012
20. Scaffold Protein Clusters
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
47. Bon Lon
50. Bon Lon Lon : 2 Bon : 10
51. Ron Bon Ron : 15 Bon : 10
52. Ron Bon
53. Ron Bon
54. Ron Bon
55. Ron Bon
56. Bon Roff
57. Bon Roff
58. Cluster Lifetimes > 1 year Cluster Lifetimes > 10 years
60. ¨  10 min: 82% ¨  30 min: 78% ¨  45 min: 66% ¨  60 min: 64% ¨  60 min low: ¤  62%
62. Work with Dan (“Berkeley Guy”)