et al., 1997). Effects of ACh on a rapid time-scale likely underlie its role in stimulus-response tasks in which subsecond reactivity is required for appropriate behavioral responses, as in prefrontal cortex-dependent cue detection (Parikh et al., 2007a) or auditory discrimination (Letzkus et al., 2011). The data indicate that differences in sites of receptor expression, affinity of ACh effects at both mAChRs and nAChRs, as well as rates of synaptic clearance (mediated through AChE activity) and local concentration of ACh in and outside the synapse, are critical for the control and specificity of cholinergic signaling. Further, differences in the time-scale of release at the local microcircuit level further refine the action of ACh in complex behaviors (reviewed in (Hasselmo and Giocomo, 2006; Sarter et al., 2009; Yu and Dayan, 2005)).
