Acetylcholine (ACh) is a neurotransmitter which was first identified by Henry Hallet Dale in 1914 who observed its interaction with heart tissue. This observation was confirmed by Otto Loewi who decided to call it 'Vagusstoff'. Why was it called this? Because it was found to be released by the vagus nerve.
They both won the 1936 nobel prize in Physiology/Medicine. Why is this important? Recently the vagus nerve has become the focus of a lot of neuroscience attention due to the effect of vagus nerve stimulation. Engineer et al (2011) and Engineer et al (2012) both demonstrated how vagus nerve stimulation can be used to condition the brain and by matching stimulation with stimuli, could effectively treat tinnitus. The research showed a remapping effect of auditory neurons. This was tested only in a mouse model but the results were so promising that a project replicating this is currently being recruited for, except to study this effect in humans.
Porter (2011) has demonstrated how matching vagus nerve stimulation with simple motor tasks allows for a remapping of the motor cortices of the mouse brain. The mechanism of action behind vagus nerve stimulation seems to be unknown.
Stimulation of the vagus nerve may release ACh into the cortex, as observed by Otto Loewi, which somehow causes a cortical plastic effect. Again though, we are faced with the question of How?
Well, ACh has long been linked to synaptic plasticity and acts either by:
Directly enhancing currents through NMDA receptors which have been associated with synaptic plasticity with specifics to memory and learning.
Indirectly suppressing adaptation; Neural adaptation, also known as 'up regulation' and 'down regulation' is the process whereby neurons stop firing as a result of constant stimulation allowing regulation to occur.
Along with these observed effects, ACh has been noted to effect heart rate which is something also noted in patients receiving vagus nerve stimulation.
It would definitely seem that rather looking at VNS and cortical plasticity...it's time to look at VNS, causing changes in ACh activity causing plasticity.