Редактирование: Whole brain emulation (раздел)

=== Unknown Neurotransmitters ===

* Not all neuromodulators are known. At present about 10 major neurotransmitters and 200+ 
neuromodulators are known, and the number is increasing. (Thomas, 2006) lists 272 
endogenous extracellular neuroactive signal transducers with known receptors, 2 gases, 19 
substances with putative or unknown binding sites and 48 endogenous substances that may 
or may not be neuroactive transducers (many of these may be more involved in general 
biochemical signalling than brain‐specific signals). Plotting the year of discovery for different 
substances (or families of substances) suggests a linear or possibly sigmoidal growth over 
time (Figure 11). 


* An upper bound on the number of neuromodulators can be found using genomics. About 800 
G‐protein coupled receptors can be found in the human genome, of which about half were 
sensory receptors. Many are “orphans” that lack known ligands, and methods of 
“deorphanizing” receptors by expressing them and determining what they bind to have been 
developed. In the middle 1990’s about 150 receptors had been paired to 75 transmitters, 
leaving around 150‐200 orphans in 2003 (Wise, Jupe et al., 2004). At present, 7‐8 receptors are 
deorphanized each year (von Bohlen und Halbach and Dermietzel, 2006); at this rate all 
orphans should be adopted within ≈20 years, leading to the discovery of around 50 more 
transmitters (Civelli, 2005). 
 
* Similarly guanylyl cyclase‐coupled receptors (four orphans, (Wedel and Garbers, 1998)), 
tyrosine kinase‐coupled receptors (<<100, (Muller‐Tidow, Schwable et al., 2004)) and cytokine 
receptors would add a few extra transmitters.  
 
* However, there is room for some surprises. Recently it was found that protons were used to 
signal in C. elegans rhythmic defecation (Pfeiffer, Johnson et al., 2008) mediated using a 
Na+/H+ exchanger, and it is not inconceivable that similar mechanisms could exist in the 
brain. Hence the upper bound on all transmitters may be set by not just receptors but also by 
membrane transporter proteins.  

* For WBE modelling all modulatory interactions is probably crucial, since we know that 
neuromodulation does have important effects on mood, consciousness, learning and 
perception. This means not just detecting their existence but to create quantitative models of 
these interactions, a sizeable challenge for experimental and computational neuroscience.