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My understanding of how neurons transmit signals is pretty basic - dendrites receive signals (both excitatory and inhibitory), transmitting them to the cell body where, if a sufficient depolarization builds up, the axon fires an action potential, sending the signal along. This entire process is carried out by various ion channels, especially voltage gated ones. My question is this - do we know how sensitive the speed and reliability of the process are to genetic variations that control how these ion channels are built? Is it robust enough to permit small variations, or is any change catastrophic? If it permits small variations, do we know how variable the human population is for features like signal fidelity (low rate for failing to fire when the neuron should, and low rate for firing in the absence of stimulus) and transmission speed?

Considering the difficulty of studying humans, is this sort of information known for mice, rats, primates, or etc?

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    $\begingroup$ Action potentials are pretty robust in most circumstances, but minor tweaks at various stages of the process, whether conduction, neurotransmitter release, or post-synaptic responses, sometimes affecting only certain populations of cells, are thought to be behind many neurological disorders and conditions, including schizophrenia, autism, epilepsy, multiple sclerosis, and some peripheral neuropathies. Of cousre many of these conditions have both environmental and genetic influences, so it is often difficult to attach a specific genetic cause. $\endgroup$ – Bryan Krause Jun 11 '17 at 21:37
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    $\begingroup$ There is a certain amount of variation in the genes that regulate ion channel/receptor structure, much of which has little/no affect on neuronal function. But as @BryanKrause says, many are known that do cause neuronal disorders. A very interesting question, but I don't know the genetics well enough to provide a decent answer. $\endgroup$ – Oliver Houston Jun 12 '17 at 15:56
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    $\begingroup$ @OliverHouston What I was trying to get at, although maybe not too clearly, is that a lot of the variation in those genes does not deterministically cause disorders, but that variation may predispose certain individuals to those disorders. For Sean: it isn't directly related to your question, but on the issue of robustness you could read some papers on multiple sclerosis. MS is a demyelinating disorder, which eventually impairs conductivity, but it actually takes quite a bit of demyelination before the symptoms are noticeable. $\endgroup$ – Bryan Krause Jun 12 '17 at 16:22
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    $\begingroup$ Got it - based on your SE background I see you are mostly a physics/math person. I would highly recommend the "NEURON" simulation which is freely available and documented in various places. There are pre-existing models that you could tweak to test some of your hypotheses. For example, if you are talking about conduction, rather than action potential initiation, you will find that one of the important factors in both threshold and reliability is voltage-gated sodium channel concentration. However, more Na+-VGCs will mean both a lower threshold and more reliable signalling. $\endgroup$ – Bryan Krause Jun 12 '17 at 16:36
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    $\begingroup$ Also note that in biology if you ask about variability: "do we know how sensitive the speed and reliability of the process are to genetic variations" - the answer is almost always going to depend somewhat on the phenotype. If a variation doesn't cause any disorder, there is no selective pressure to prevent that type of variation, so over generations that variation will tend to increase on average. The presence of some low-efficacy genetic causes for some of the disorders I mentioned is good evidence that there is some variability in the population, though. $\endgroup$ – Bryan Krause Jun 12 '17 at 16:38

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