Acetylcholine: I. Muscarinic receptors

The study of brain muscarinic receptors began more than a century ago, long before the existence of muscarinic receptors was postulated and then demonstrated. However, the effects of drugs acting on these receptors, such as atropine, eserine, pilocarpine and arecoline have already been studied. This chapter is an overview of these studies with the purpose of defining the roles that different subtypes of muscarinic receptors play in the cognitive process. Background information on the anatomy of the brain cholinergic system, the muscarinic receptors subtypes, their transduction mechanisms and their distribution are discussed. The distribution of the receptors is influenced by behavior, and age, and Alzheimer’s disease (AD). Three approaches have been used in order to understand which cognitive processes depend on the activation of muscarinic receptors: i) blockade of the receptors, ii) lesions of the cholinergic pathways and iii) the attempt to correlate the cognitive process with changes in cholinergic neuron activity. From these studies, it may be concluded that muscarinic receptors appear to represent a widespread target system through which acetylcholine, released from the cholinergic network, improves memory performance by augmenting the selectivity of perceptual processing during encoding. Finally, the possibility to correct the cognitive deficits accompanying AD and aging by acting directly or indirectly on muscarinic receptors is examined.