Developmental aspects of the cholinergic system

Beyond its importance in sustaining or modulating different aspects of the activity of the central nervous system (CNS), the cholinergic system plays important roles during development. In the current review, we focus on the developmental aspects associated with major components of the cholinergic system: Acetylcholine, choline acetyltransferase, vesicular acetylcholine transporter, high-affinity choline transporter, acetylcholinesterase, nicotinic and muscarinic receptors. We describe when and where each one of these components is first identified in the CNS and the changes in their levels that occur during the course of prenatal and postnatal development. We also describe how these components are relevant to many events that occur during the development of the CNS, including progenitor cells proliferation and differentiation, neurogenesis, gliogenesis, neuronal maturation and plasticity, axonal pathfinding, regulation of gene expression and cell survival. It will be noticed that evidence regarding the developmental aspects of the cholinergic system comes mostly from studies that used agonists, such as nicotine, and antagonists, such as hemicholinium-3. Studies using immunohistochemistry and genetically altered mice also provided valuable information.