The two primary sources of ACh in the brain include projection neurons that innervate distal areas and local interneurons that are interspersed among their cellular targets. Cholinergic projection neurons are found in nuclei throughout the brain, such as the pedunculopontine and laterodorsal tegmental areas (PPtg and LDTg), the medial habenula (MHb) (Ren et al., 2011), and the basal forebrain (BF) complex (Mesulam, 1995; Zaborszky, 2002; Zaborszky et al., 2008), including the medial septum (MS). These cholinergic neurons project widely and diffusely, innervating neurons throughout the CNS. Cholinergic interneurons are typified by the tonically-active ACh neurons of the striatum and nucleus accumbens, and there is some indication from anatomical studies that cholinergic interneurons are present in the rodent and human neocortex, but not the non-human primate cortex (Benagiano et al., 2003; Mesulam, 1995; von Engelhardt et al., 2007). The actions of ACh released from both populations of cholinergic cells are mediated through pre- and postsynaptic receptors on a large variety of neuronal subtypes throughout the brain, and it should be noted that cholinergic inputs contribute to cortical and hippocampal function across phylogeny.
