Increasing evidence suggests that ACh signaling in a number of brain areas is important for stress responses (Figure 4). In addition to the well-documented role of the hippocampus in learning and memory, the amygdala in mediating fear responses and the PFC in attention, these brain areas are critical nodes in adaptation and responses to stress (Belujon and Grace, 2011; Gozzi et al., 2010; McGaugh, 2004; Sapolsky, 2000; Tottenham and Sheridan, 2009). Dysfunction in the activity of these regions is strongly implicated in major depressive disorder (Sheline et al., 1998; Videbech and Ravnkilde, 2004). The hippocampus, amygdala and PFC receive a very high level of cholinergic input that come from the BF complex, and in particular, from the medial septum and nucleus basalis, respectively (Mesulam, 1995). Several studies have shown that stress increases ACh release in a brain region-specific manner (Mark et al., 1996). For instance, hippocampal and cortical ACh levels can increase following restraint stress in rats, while ACh levels in the amygdala are unchanged, although an increase in amygdalar cholinergic tone can also reduce BLA activity though activation of
