et al., 2012), highlighting the fact that ACh can induce heterogeneous effects in different brain areas that appear to have opposite behavioral consequences. The behavioral effect of ACh signaling in vivo likely depends on the baseline conditions in the particular circuit of interest at the time of ACh release, and is the result of integration of its, sometimes conflicting, effects in different circuits. More studies are necessary to determine whether preclinical studies of cholinergic signaling in hippocampus, PFC and/or amygdala can be linked to the effects of ACh in human subjects, and to identify physiological mechanisms that are essential for these effects on behaviors related to mood and affect.