ReDiClus

Receptor Diffusion & Cluster Model - ReDiClus Model

Diffusion and Cluster Model of LTP

Model Space

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

'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

two independent 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: ^FIG:{{#info: {{{2}}} CLICK AWAY FROM IMAGE TO CLOSE }}; ^FIG:{{#info: {{{2}}} CLICK AWAY FROM IMAGE TO CLOSE }}

Quantitative Physiology of the Dendrite

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.

Mouse over to see the visual: ^FIG:{{#info: Error creating thumbnail: File missing{{{2}}} CLICK AWAY FROM IMAGE TO CLOSE }}

• 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

{{{2}}}

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.