Do Nicotinic Receptors Modulate High-Order Cognitive Processing?

Highlights

• nAChRs are oligomers composed of several categories of subunits, which determine their physiology and pharmacology in the brain.

• Cholinergic signaling through nAChRs modulate cognition and conscious awareness.

• The contribution of nAChRs oligomers to high-order cognitive processing has been investigated using genetically modified mice, which revealed, among other findings, that β2-subunit-containing nAChRs modulate sleep and anesthesia as well as several high-order cognitive functions.

• In humans, administration of nicotine ameliorates cognitive impairment such as deficits in attention, social interactions, and working memory and thus has a positive action on high-order cognitive processes.

• Conversely, repeated exposure to nicotine creates nicotine addiction and, consequently, loss of cognitive control and neural circuit impairments.

• Human genetic studies have identified variants in nAChRs that predispose individuals to neuropsychiatric diseases such as schizophrenia. Genetic, molecular, and mechanistic studies of the contribution of specific nicotinic subunits to mental disorders and neurodegenerative diseases is a promising strategy to unravel the involvement of nAChRs in the development of these pathologies and could provide targets for developing efficient pharmacological treatments.

Recent studies provided strong evidence that deficits in cholinergic signaling cause disorders of cognition and affect conscious processing. Technical advances that combine molecular approaches, in vivo recordings in awake behaving animals, human brain imaging, and genetics have strengthened our understanding of the roles of nicotinic acetylcholine receptors (nAChRs) in the modulation of cognitive behavior and network dynamics. Here, we review the emergent role of nAChRs in high-order cognitive processes and discuss recent work implicating cholinergic circuits in cognitive control, including conscious processing.