Nicotinic receptors function as non-selective, excitatory cation channels (Changeux et al., 1998; Picciotto et al., 2001) and occur as homomeric or heteromeric assemblies of a large family of α- and β-subunits (α2-α7 and β2-β4; reviewed in (Picciotto et al., 2000)). While neuromodulators are typically associated with metabotropic signaling, the role of the ionotropic nAChRs in the brain appears to be largely modulatory as well (Picciotto, 2003). For example, nAChRs are not clustered at postsynaptic membranes apposed to sites of ACh release, but are rather dispersed along the surface (and intracellular compartments) of neurons, including presynaptic terminals (McGehee et al., 1995; Vidal and Changeux, 1993), cell bodies and even axons (Arroyo-Jimenez et al., 1999; Hill Jr. et al., 1993; Kawai et al., 2007). In addition, stimulation of nAChRs can increase the release of glutamate, GABA, dopamine (DA), ACh, norepinephrine, and serotonin (McGehee et al., 1995; Wonnacott, 1997) (Figure 1). Nicotinic modulation of neurotransmitter release is often subtype-specific and this specificity can vary across brain areas, with distinct nAChRs coupling to release of glutamate (α7) vs. GABA (α4β2*) (Mansvelder et al., 2002)
