Acetylcholine (ACh) is known to exert profound modulatory effects on information processing in the brain. For example, experimental blockade of cholinergic transmission can lead to defects in memory and cognitive function, and loss of cerebral cholinergic innervation occurs in Alzheimer's disease. This latter cholinergic deficit contributes, at least in part, to the dementia seen in Alzheimer's patients. The development of antibodies to choline acetyltrarfsferase (ChAT), the synthesizing enzyme for ACh, allowed for specific visualization of cholinergic neurons and immunohistochemical studies have revealed two major ascending cholinergic systems that are likely to mediate the behavioral effects of ACh: The magnocellular basal forebrain and mesopontine tegmental cholinergic groups. More recently, the availability of molecular probes to visualize neuronal populations expressing ChAT mRNA have confirmed the identity of these cell groups, as well as other major cholinergic neuronal populations in the nervous system. This chapter describes the current level of understanding concerning the functional organization of the ascending cholinergic pathways cited above, as well as addressing some issues relating to the identification of trophic mechanisms that support the viability of the basal forebrain system. This latter topic bears special relevance to cholinergic dysfunction in disease and is considered in more detail in elsewhere in this volume. While the present focus is on ascending cholinergic pathways, it is important to bear in mind that these pathways represent part of a larger group of so-called diffuse ascending systems, including dopaminergic, noradrenergic, serotonergic and histaminergic transmitter systems. All of these pathways exert important modulatory effects on information processing in the nervous system and are likely to interact significantly with one another.
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