ReDiClus

Receptor Diffusion & Cluster Model - ReDiClus Model

Diffusion and Cluster Model of LTP

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Diffusion and Cluster Model of LTP

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Model Space

The model is simulated in a 3D space with the following parameters

• There is a 3D XYZ coordinate grid
• The X-Y plane has 60x60 area
• The X-Y plane consists of real numbers: -30 to +30
• The Z axis is only 2 levels: 0 and -1
  • 0 represents the membrane surface
  • -1 represents intracellular space

Particle Types

There are 2 types of particles in the simulation

• 'Red' particle dots represent AMPA receptors
  • Red dots can randomly diffuse anywhere on the X-Y plane
  • Red dots only diffuse on the surface Z = 0
• 'Blue' particle dots represent PSD-95 molecules
  • Blue dots are contained in predefined PSD areas and cannot leave
  • Blue dots can exist at the surface Z = 0 or intracellularly Z = -1

Visual Representations

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two independent processes

In this model, there are two independently occurring processes.

• 1. Blue dots can be expressed at the surface or internalized within their PSD area
  • The Blue dot internalization/externalization rate properties are set by the Shouval cluster model equations.
• 2. Red dots diffuse on the X-Y plane with brownian motion
  • Each Red dot has an initial step size randomly drawn from a normal distribution with a mean = 1 and sd = .2

The step size for Red dots is dynamically altered when it's located in a PSD area

• In a PSD, the step size is reduced by a by some factor based on the number of Blue dots currently expressed at the surface of that PSD
• The more Blue dots at the surface, the more the step size is reduced
• The current step size function is:
  • f(R_step) = R * (10*(1 ⁄ B_n))
    • where R_step is the baseline Red dot step size
    • where B_n is number of Blue dots currently expressed at the PSD surface

Several screen shots of the dynamic graphs in the model

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Quantitative Review

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Quantitative Physiology of the Dendrite

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The Size of Dendrites

• Dendrite: 1–10 spines per μm
• Spines: 0.5–2 μm in length
• PSD: 100 - 300 nm diameter • PSD: 10,000 proteins (or 100 copies of 100 proteins)
• CaMKIIα: 7.4%
• CaMKIIβ: 1.3%
• SynGap: 2.1 pmol/20 μg
• NMDAR: 20 proteins
• AMPAR: 15 proteins • GluR: 60 subunits, 15 tetramers, 80% or 12 GluR1/GluR2 heteromers
• PSD95: within 12 nm of surface

• adapted from: Sheng and Hoogenraad (2007) The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem, 76:823-47.

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• Diffusion rate was measured as µm²/s
• Below are the linearized median diffusion rates
• Dendrite: 0.8 µm/s
• PSD: 0.4 - 0.1 µm/s
• PSDp: 0.1 - 0.01 µm/s

• from: Choquet et al (2010) CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron

Choquet 2007 Real Time Receptor Diffusion

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Choquet 2007 Real Time Receptor Diffusion Analysis

• The video represents a 10µm × 10µm section scaled to a 535px × 535px video.
  • 1_µm : 53.5_px
• The analysis below documents one instance of Qdot diffusion, between the 6s-7s time points.
• This instance was chosen because of the clarity of motion and no Qdot flicker.
• The Qdot (center) moves from pixel location (X:291, Y:302) at 6.78s to (X:319, Y346) at 6.98s
  • That is a distance of 52.2px in 200ms
  • Qdot velocity: Q_v ≈ 1_µm ⁄ 200_ms
  • Note this diffusion rate of 5µm/s is 10-fold higher than the median diffusion rate reported above.
  • An upper bound of 5µm/s means that receptors can move between synapses in fractions of a second.

Figures:

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Receptor Diffusion Rate Best Estimates

• GABAA: .01 - .05 µm²/s ^FIG: {{#info: Choquet 2010 CLICK AWAY FROM IMAGE TO CLOSE }}

Malinow

Molecular Methods

Quantum Dots

Choquet

AMPAR