Evolution in Neuromodulation—The Differential Roles of Acetylcholine in Higher Order Association vs. Primary Visual Cortices

This review contrasts the neuromodulatory influences of acetylcholine (ACh) on the relatively conserved primary visual cortex (V1), compared to the newly evolved dorsolateral prefrontal association cortex (dlPFC). ACh is critical both for proper circuit development and organization, and for optimal functioning of mature systems in both cortical regions. ACh acts through both nicotinic and muscarinic receptors, which show very different expression profiles in V1 vs. dlPFC, and differing effects on neuronal firing. Cholinergic effects mediate attentional influences in V1, enhancing representation of incoming sensory stimuli. In dlPFC ACh plays a permissive role for network communication. ACh receptor expression and ACh actions in higher visual areas have an intermediate pro file between V1 and dlPFC. This changing role of ACh modulation across association cortices may help to illuminate the particular susceptibility of PFC in cognitive disorders, and provide therapeutic targets to strengthen cognition.