Although cholinergic interneurons (CINs) are 2-5% of all striatal neurons, they establish an extensive arrangement of axons and form a diffuse neurotransmission system (Descarries et al., 1997; Descarries and Mechawar, 2000). Therefore, cholinergic activity in the striatum has long been hypothesized to play a role in the modulation of DA release (Giorguieff et al., 1976; Zhou et al., 2001; Zhang and Sulzer, 2004; Threlfell et al., 2010). Genetic deletion or pharmacological manipulation studies of nicotinic cholinergic (nAChRs) as well as muscarinic (mAChRs) receptors, have shown that they modulate electrically-evoked DA release in the striatum (Exley et al., 2012; Zhou et al., 2001; Exley et al., 2008, 2011; Zhang et al., 2009; Threlfell et al., 2010). Moreover, nAChR-targeted drugs differentially alter DA release in a frequency-dependent manner. This finding has led to the notion that a “high-pass” filter dependent on antagonism of nAChRs or nicotine, facilitates burst release of DA (Exley and Cragg, 2008), an activity pattern observed mainly following the presentation of reward and reward-predicting cues (Mirenowicz and Schultz, 1996; Nakahara et al., 2004; Roesch et al., 2007; Schultz, 2007; Apicella et al., 1991).
