Distribution of Cholinergic Neurons in Human Brain

Acetylcholine (ACh) was the first neurotransmitter to be identified, ushering in the modern concept of chemical transmission in the nervous system. Nevertheless, for many years information regarding cholinergic pathways, particularly in the central nervous system, lagged behind several other neurotransmitters because of technical difficulties in cellular localization of cholinergic structures. Initial information came from measurements of the effects of various lesions on the levels of ACh or its specific synthesizing enzyme, choline acetyltransferase (ChAT), and from histochemical studies on the degrading enzyme, acetylcholinesterase (AChE)1. The best early application of the latter method was in the papers of Shute and Lewis 2,3. Unfortunately, although AChE has a relatively high concentration in known cholinergic structures4-8, it also occurs in non-cholinergic cells8-9. Suppression of AChE with DFP has done much to separate cholinergic from non-cholinergic AChE-containing cells5-10 but, since some of the latter contain anomalously high concentrations of AChE, the method cannot be relied upon as a definitive method for identifying cholinergic structures. Moreover, the DFP pretreatment suppresses fiber staining, thus reducing the potential for tracing pathways. A more definitive method depends upon immunohistochemical staining using antibodies to the selective enzyme, ChAT11. Although the purification of ChAT has been fraught with difficulty and many of the antibodies prepared are of relatively low titer, the method has allowed much to be learned about ChAT-containing structures in the brain. Much fundamental information remains to be elicited and a number of controversies have developed around existing reports, but the data already available have permitted new insights into cholinergic pharmacology and the relationship between a number of disease processes and cholinergic systems.