科研之友
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摘要
The primate dorsolateral prefrontal cortex (dlPFC) subserves top-down regulation of attention and working memory abilities. Depletion studies show that the neuromodulator acetylcholine (ACh) is essential to dlPFC working memory functions, but the receptor and cellular bases for cholinergic actions are just beginning to be understood. The current study found that nicotinic receptors comprised of alpha 4 and beta 2 subunits (alpha 4 beta 2-nAChR) enhance the task-related firing of delay and fixation cells in the dlPFC of monkeys performing a working memory task. Iontophoresis of alpha 4 beta 2-nAChR agonists increased the neuronal firing and enhanced the spatial tuning of delay cells, neurons that represent visual space in the absence of sensory stimulation. These enhancing effects were reversed by coapplication of a alpha 4 beta 2-nAChR antagonist, consistent with actions at alpha 4 beta 2-nAChR. Delay cell firing was reduced when distractors were presented during the delay epoch, whereas stimulation of alpha 4 beta 2-nAChR protected delay cells from these deleterious effects. Iontophoresis of alpha 4 beta 2-nAChR agonists also enhanced the firing of fixation cells, neurons that increase firing when the monkey initiates a trial, and maintain firing until the trial is completed. These neurons are thought to contribute to sustained attention and top-down motor control and have never before been the subject of pharmacological inquiry. These findings begin to build a picture of the cellular actions underlying the beneficial effects of ACh on attention and working memory. The data may also help to explain why genetic insults to alpha 4 subunits are associated with working memory and attentional deficits and why alpha 4 beta 2-nAChR agonists may have therapeutic potential.
- 出版日期2017-5-24
- 单位北京大学
