Редактирование: Whole brain emulation (раздел)

=== Volume Transmission ===

Surrounding the cells of the brain is the extracellular space, on average 200 Å across and 
corresponding to 20% of brain volume (Nicholson, 2001). It transports nutrients and buffers 
ions, but may also enable volume transmission of signalling molecules.  

* Volume transmission of small molecules appears fairly well established. Nitrous oxide is 
hydrophobic and has low molecular weight and can hence diffuse relatively freely through 
membranes: it can reach up to 0.1‐0.2 mm away from a release point under physiological 
conditions (Malinski, Taha et al., 1993; Schuman and Madison, 1994; Wood and Garthwaite, 
1994). While mainly believed to be important for autoregulation of blood supply, it may also 
have a role in memory (Ledo, Frade et al., 2004). This might explain how LTP (Long Term 
Potentiation) can induce “crosstalk” that reduces LTP induction thresholds over a span of 10 
μm and ten minutes (Harvey and Svoboda, 2007). 

* Signal substances such as dopamine exhibit volume transmission (Rice, 2000) and this may 
have effect for potentiation of nearby synapses during learning: simulations show that a 
single synaptic release can be detected up to 20 μm away and with a 100 ms half‐life (Cragg, 
Nicholson et al., 2001). Larger molecules have their relative diffusion speed reduced by the 
limited geometry of the extracellular space, both in terms of its tortuosity and its anisotropy 
(Nicholson, 2001). As suggested by Robert Freitas, there may also exist active extracellular 
transport modes. Diffusion rates are also affected by local flow of the CSF and can differ from 
region to region (Fenstermacher and Kaye, 1988); if this is relevant then local diffusion and 
flow measurements may be needed to develop at least a general brain diffusion model. The 
geometric part of such data could be relatively easily gained from the high resolution 3D 
scans needed for other WBE subproblems. 

* Rapid and broad volume transmission such as from nitrous oxide can be simulated using a 
relatively coarse spatiotemporal grid size, while local transmission requires a grid with a 
spatial scale close to the neural scale if diffusion is severely hindered.  

* For constraining brain emulation it might be useful to analyse the expected diffusion and 
detection distances of the ≈200 known chemical signalling molecules based on their molecular 
weight, diffusion constant and uptake (for different local neural geometries and source/sink 
distributions). This would provide information on diffusion times that constrain the diffusion 
part of the emulation and possibly show which chemical species need to be spatially 
modelled.