The neocortex plays a crucial role in all cognitive functions. This is accomplished through connections between neuronal networks which emerge from synaptic interactions of many neuron types. Inhibitory interneurons constitute a sparse but crucial neuronal class which coordinate cortical activity. Inhibitory circuits are controlled by different neuromodulators. Among them, the neurotransmitter acetylcholine highly controls cortical activity by signaling through two classes of receptors: the ionotropic nicotinic receptors and the metabotropic muscarinic receptors. Cortical acetylcholine signaling shapes neuronal circuit dynamics and underlies specific aspects of cognitive functions and behaviors including attention, learning, memory, perception and motivation. 

Thus, it is not surprising that acetylcholine receptor gene variants are strongly linked to psychiatric disorders such as schizophrenia and neurodegenerative disorders such as Alzheimer’s disease. Evidence identified that cortical inhibitory circuits and cholinergic neurotransmission are affected in psychiatric disorders, however, the actual interplay between these two systems is unknown.