Central Cholinergic Pathways Neuroanatomy and Some Behavioral Implications

Abstract

Neurons which synthesize and secrete acetylcholine (ACh) for the purpose of neurotransmission are designated as cholinergic. The pioneering work of Otto Loewi established ACh as a neurotransmitter in the peripheral nervous system (Loewi, 1921). Soon thereafter, the suggestion was made that ACh could also serve a similar purpose in central nervous structures (Dale, 1938). Partial support for this possibility was obtained by pharmacological and physiological investigations which showed that ACh, acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and cholinergic receptor sites were widely distributed throughout the neuraxis and that many central neurons were responsive to ACh (for review see Silver, 1974; Fibiger, 1982; Mesulam et al., 1983b). Observations based on AChE histochemistry provided additional information on the anatomical arrangement of cholinergic pathways in the brain stem, diencephalon, limbic system, and neocortex (Krnjevic and Silver, 1965; Shute and Lewis, 1967). However, uncertainty has always been associated with conclusions based on AChE histochemistry since this enzyme is also present in many noncholinergic neurons. The production of monoclonal and monospecific antibodies to ChAT by several research groups has now provided new and much more reliable information on the distribution of cholinergic neurons and on the organization of their connections (Rossier, 1984; Wainer et al., 1984). Since the presence of ChAT is necessary and probably also sufficient for the synthesis of ACh, the immunohistochemical demonstration of ChAT currently constitutes the most specific anatomical marker for putative cholinergic neurons and their pro¬cesses. Although it is not yet known if all neurons that contain ChAT also secrete ACh, this seems like a reasonable assumption to make, but will ultimately need definitive confirmation through a combination of anatomical and physiological approaches. The contemporary literature on the anatomy of cholinergic neurons is vast and varied. The purpose of this chapter is not to provide a critical review of these developments but to summarize some observations on central cholinergic pathways that my colleagues and I have made in the past 10 years. The papers cited provide additional references to the rich literature on this subject.