Roles of cholinergic receptors during attentional modulation of cue detection

Abstract

Basal forebrain corticopetal cholinergic neurons are known to be necessary for normal attentional processing. Alterations of cholinergic system functioning have been associated with several neuropsychiatric diseases, such as Alzheimer’s disease and schizophrenia, in which attentional dysfunction is thought to be a key contributing factor. Loss of cortical cholinergic inputs impairs performance in attention-demanding tasks. Moreover, measures of acetylcholine with microdialysis and, more recently, of choline with enzyme-coated microelectrodes have begun to elucidate the precise cognitive demands that activate the cholinergic system on distinct time scales. However, the receptor actions following acetylcholine release under attentionally-challenging conditions are only beginning to be understood. The present review is designed to summarize the evidence regarding the actions of acetylcholine at muscarinic and nicotinic receptors under cognitively challenging conditions in order to evaluate the functions mediated by these two different cholinergic receptor classes. Moreover, evidence that supports beneficial effects of muscarinic muscarinic-1 receptor agonists and selective nicotinic receptor subtype agonists for cognitive processing will be discussed. Finally, some challenges and limitations of targeting the cholinergic system for treating cognitive deficits along with future research directions will be mentioned. In conclusion, multiple aspects of cholinergic neurotransmission must be considered when attempting to restore function of this neuromodulatory system.

Keywords: 192 IgG-saporin, Acetylcholinesterase inhibitors, Alzheimer’s disease, Attention, Basal forebrain, Muscarinic, Nicotinic, Protein kinase C, Prefrontal cortex, Schizophrenia

Core tip: The corticopetal cholinergic system is critical for normal attentional processing. Disruption of this system is associated with cognitive deficits in several disorders. Thus, restoration of cortical cholinergic neurotransmission represents a reasonable target for treating some cognitive disorders. Evidence is presented that the muscarinic muscarinic-1 receptor and nicotinic receptor subtypes appear to be key targets for future investigations related to treating cognitive disorders. Future research into muscarinic-nicotinic receptor interactions, along with the role of second messenger systems, is needed to further develop appropriate strategies for restoring cortical cholinergic neurotransmission.