(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) or DA (α4/α6β2*) vs. ACh (α3β4*) (Grady et al., 2001) in the VTA, while β2* nAChRs can modulate the release of glutamate from thalamo-cortical projections (Parikh et al., 2010). Presynaptic effects of nAChRs contribute to synaptic plasticity in the VTA (Mansvelder and McGehee, 2000; Wooltorton et al., 2003), hippocampus (Ge and Dani, 2005; Ji et al., 2001; Radcliffe and Dani, 1998), and prefrontal cortex (Couey et al., 2007). In addition, nAChRs may also be important for synchronizing neuronal activity. For example, nicotine is reported to coordinate firing of thalamocortical fibers through effects on nAChRs in white matter (Bucher and Goaillard, 2011; Kawai et al., 2007). Despite the clear effects of presynaptic nAChRs in electrophysiological studies, their relationship to the behavioral consequences of nicotine administration is not completely understood. For example, although nicotine stimulates the firing of DA neurons through actions in the ventral tegmental area (VTA) and increases release of DA from the midbrain projections to the NAc through actions
