摘要
Basal forebrain corticopetal cholinergic neurons are known to be necessary for normal attentional process-ing. 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 contrib-uting 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 acetyl-choline release under attentionally-challenging condi-tions 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, evi-dence 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 defcits 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.
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.
基金
Supported by AG030646 and the Jeffress Memorial Trust
