Despite a great deal of progress, there are still critical gaps in our understanding of the dynamics of ACh release from different neuronal populations, how that changes in response to environmental conditions such as metabolic need or stress, and how far from the site of release ACh can diffuse in different brain areas. While novel tools will allow more precise stimulation of ACh release, the patterns of release will not be optimal unless there is a better understanding of the physiological patterns of firing. The ability to mimic patterns of ACh release in vivo will be critical for identifying the physiological effects of cholinergic neuromodulation, and distinguishing the actual, from the possible, effects of ACh in the brain.
