Nicotinic signaling in development

Abstract

Nicotinic acetylcholine receptors (nAChRs) appear early in development, reaching their highest relative levels in early postnatal life. They are expressed on nearly every neuron in the central nervous system (CNS) and in many nonneuronal cell-types as well. Cholinergic neurons not only appear early on, but also project to many brain regions at this time. These events largely precede the bulk of glutamatergic synapse formation and the maturation of GABAergic transmission. As a result cholinergic nicotinic signaling is temporally and spatially positioned to have a substantial impact on maturation of the nervous system and the formation of neural nets. This chapter will review recent fi ndings indicating that endogenous nicotinic input is required for normal maturation of the nervous system and that excessive or altered nicotinic signaling at early times can produce signifi cant aberrations in the synaptic pathways that form. First we summarize the nAChR subtypes, their appearance and distribution during development, and discuss the positioning and abundance of cholinergic neurons and their projections to potential synaptic targets. Next we consider the kinds of nicotinic signaling found early in development, including spontaneous waves extending across large regions, and discuss the organizational impact this is likely to have. We then address the role that nicotinic signaling has in driving the conversion of GABAergic signaling from the excitatory mode found in early postnatal life to the inhibitory mode characteristic of the adult. Lastly we review recent results demonstrating that endogenous nicotinic signaling is required during early postnatal life to achieve normal numbers of glutamatergic synapses in the adult and shape the neural networks that form. Disruption of these events is likely to have long-lasting consequences, perhaps accounting for many of the behavioral defi cits found in adults after early disruption or abuse of nicotinic cholinergic signaling.