In contrast, mAChRs located on pyramidal cell axon terminals suppress cortico-cortical transmission (Gil et al., 1997; Hsieh et al., 2000; Kimura and Baughman, 1997; Oldford and Castro-Alamancos, 2003). Moreover, the ACh-mediated increased excitability of dendrite-targeting interneurons described above likely contributes to reduced efficacy of intra-cortical communication. The simultaneous enhancement of feed-forward inputs from the thalamus through cholinergic actions on parvalbumin-positive interneurons, and suppression of intra-cortical feed-back inputs through effects on dendrite-targeting interneurons, may increase the “signal-to-noise” ratio in cortical networks, making neurons more sensitive to external stimuli. In keeping with this view, mAChR activation strongly suppresses the spread of intra-cortical activity, leaving responses to thalamic inputs relatively intact (Kimura et al., 1999). Intriguingly, in the prefrontal cortex, the expression of nicotinic receptors in deep pyramidal cells may produce layer-specific cholinergic modulation, selectively enhancing activity of output neurons (Poorthuis et al., 2012).
