Neurotransmitter regulation of neural development: acetylcholine and nicotinic receptors

Abstract

Several neurotransmitter systems have been related to developmental processes during the past decade. In this review, we discuss the evidence that the nicotinic acetylcholine receptors could have an additional function during development that may be unrelated to their role in cholinergic neurotransmission in the vertebrate brain. Both temporal expression data and in vitro and in vivo studies with nicotinic agonists and antagonists have provided direct support for a role of nicotinic receptors in neural developmental processes such as neurite outgrowth and differentiation. A similar picture has emerged for other neurotransmitter and receptor systems as well, which generates a new view of neural processes during both development and mature life.

The development of nicotinic receptors in the human medulla oblongata: Inter-relationship with the serotonergic system

“…This observation suggests that α4 plays a trophic role upon at least a subset of rhombic lip precursors. In embryonic and fetal development, acetylcholine and nicotine via nAChRs experimentally influence neuronal cell proliferation, migration, survival, and differentiation (Opanashuk et al, 2001; Torrao and Britto, 2002). Functional nAChRs are present on stem and progenitor cells in the cerebral cortex of the mouse as early as embryonic day 10 (Schneider et al, 2002).…”

Autism as a disorder of neural information processing: directions for research and targets for therapy

“…In mice, knockout of the α 4 nicotinic subunit produces reduced antinociception and increased anxiety [154,171]; abnormal pain sensitivity and anxiety both are features of the autistic syndrome. In addition, nicotinic receptors are essential for normal early synaptic development [75,231] and thus nicotinic dysfunction may produce abnormal neural microarchitecture.…”

Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum

“…The same transmitter may influence multiple genes. Classical neurotransmitters such as ACh, DA, NA, 5-HT and GABA are present in concentration gradients in tissues and seem to act as developmental signals in various animal species (Lauder and Schambra, 1999;Torrao and Britto, 2002). Their regulatory roles exist throughout ontogenesis, including stages prior to development of the CNS (Lauder and Schambra, 1999).…”

“…The early expression of nAChRs and the high Ca 2+ permeability suggest a role for nAChRs in regulation and expression of early genes such as c-fos (Greenberg et al, 1986). Stimulation of neuronal nAChRs may also contribute to pathfinding and target selection during axonal outgrowth and synapse formation (Candy et al, 1985;Lipton and Kater, 1989;Kinney et al, 1993;Zheng et al, 1994;Coronas et al, 1998;Coronas et al, 2000;Torrao and Britto, 2002). The release of ACh increases in contact with a presumptive postsynaptic cell (Xie and Poo, 1986) which may activate nAChRs on the growth cone, altering the level of intracellular Ca 2+ and thereby halting the movement of the growth cone motility and stabilizing the location (Kwong et al, 2000).…”