Rationale: The prefrontal cortex (PFC) mediates executive functions, a set of control processes that optimize performance on cognitive tasks. It enables appropriate decision-making and mediates adapted behaviors, all processes impaired in psychiatric or degenerative disorders. Key players of normal functioning of the PFC are neurotransmitter (NT) systems arising from subcortical nuclei and targeting PFC subareas and, also, neuronal nicotinic acetylcholine receptors (nAChRs). These ion channels, located on multiple cell compartments in all brain areas, mediate direct cholinergic transmission and modulate the release of NTs that cross onto PFC neurons or interneurons.
Objective: We compiled current knowledge concerning the role of nAChRs in NT release, focusing on the PFC. We point out plausible mechanisms of interaction among PFC circuits implicated in executive functions and emphasized the role of β2-containing nAChRs, the high-affinity receptors for acetylcholine (ACh). These receptors are more directly implicated in behavioral flexibility either when located on PFC neurons or in the monoaminergic or cholinergic systems targeting the PFC.
Results: We shed light on potentially crucial roles played by nAChRs in complex interactions between local and afferent NTs. We show how they could act on cognition via PFC networks.
Conclusions: nAChRs are crucial for decision-making, during integration of emotional and motivational features, both mediated by different NT pathways in the PFC. We review the knowledge recently gained on cognitive functions in mice and our current understanding of PFC NT modulation. The combination of these data is expected to provide new hypotheses concerning the role of AChRs in cognitive processes.