for DA neuron activity to produce its postsynaptic effects. Reward-related activity of CINs consists of several phases (initial rise, pause, and second rise) (Morris et al., 2004; Aosaki et al., 1994; Shimo and Hikosaka, 2001; Apicella et al., 1991, 2011; Apicella, 2007). In response to reward, the peak of the initial phase coincides with the rise in DA neuron activity. We speculate that the initial rise phase of CIN firing rate and subsequent ACh-Glu release could act as a priming event, exciting MSN neurons and boosting DA release originating from the midbrain, whereas the transition to the pause in CIN activity may allow for the hypothesized contrast enhancement of the midbrain signal (Zhang and Sulzer, 2004; Cragg, 2006; Nicola et al., 2004). Moreover, activation of nAChRs promotes long-term depression of corticostriatal glutamatergic transmission via regulation of DA release (Partridge et al., 2002), and thus our findings provide evidence of a link between CIN activity and synaptic plasticity implicated in reinforcement learning. Our results generate a novel conceptual framework with which to interpret the regulation of accumbal DA release and its role in reward-directed behaviors.
