Distribution of Cholinergic Neurons in the Mammalian Brain with Special Reference to their Relationship with Neuronal Nicotinic Acetylcholine Receptors

Abstract

A cholinergic neuron, i.e., a neuron which utilizes acetylcholine (ACh) as a neurotransmitter, has several specific neurochemical features: a releasable pool of ACh; the enzyme necessary for ACh synthesis, i.e., choline acetyl-transferase (ChAT); the uptake sites for choline; and the vesicular ACh transporter (VAChT). In addition, acetylcholine esterase (AChE), the enzyme responsible for ACh degradation to acetate and choline, has long been considered a marker of cholinergic neurons. However, the simple presence of AChE cannot be considered as a good marker of cholinergic neurons, since AChE is expressed in both cholinergic and cholinoceptive cells (i.e., cells which respond to ACh) and, in some neuronal systems, is released and acts as an intercellular signal by itself. Still, neurons exhibiting high AChE activity following treatment with diisopropylphosphorofluoridate, an AChE inhibitor, are in most cases authentic cholinergic neurons (BUTCHER and WOOLF 1984). The histological techniques which have proved to be more specific, and with optimal spatial resolution, for identifying cholinergic neurons are immunocy-tochemistry using specific ChAT antibodies and in situ hybridization using probes for ChAT mRNA. Tract-tracing and lesion techniques coupled with ChAT immunohistochemistry have given the most reliable information for delineating the distribution of cholinergic pathways. By using these techniques, several cholinergic neuronal systems have been characterized in the CNS and peripheral ganglia. In view of the large amount of data available in these species, our description will be focused on the rodent nervous systems (BUTCHER 1995; WOOLF 1991; and references therein) (Fig. 1).