Cholinergic neuromodulation is known to play a key role in visual working memory (VWM) – keeping relevant stimulus representations available for cognitive processes for short time periods (up to a few minutes). Despite the growing body of evidence on how the neural and cognitive mechanisms of VWM dynamically change over retention time, there is mixed evidence available on cholinergic effects as a function of VWM delay period in non-human primates. Using the delayed matching to sample VWM task in rhesus macaques (N = 6), we aimed to characterize VWM maintenance in terms of performance changes as a function of delay duration (across a wide range of delays from 1 to 76 s). Then, we studied how cholinergic neuromodulation influences VWM maintenance using the muscarinic receptor antagonist scopolamine administered alone as transient amnestic treatment, and in combination with two doses of the acetylcholinesterase inhibitor donepezil, a widely used Alzheimer’s medication probing for the reversal of scopolamine-induced impairments. Results indicate that scopolamine-induced impairments of VWM maintenance are delay-dependent and specifically affect the 15−33 s time range, suggesting that scopolamine worsens the normal decay of VWM with the passage of time. Donepezil partially rescued the observed scopolamine-induced impairments of VWM performance. These results provide strong behavioral evidence for the role of increased cholinergic tone and muscarinic neuromodulation in the maintenance of VWM beyond a few seconds, in line with our current knowledge on the role of muscarinic acetylcholine receptors in sustained neural activity during VWM delay periods.

已知胆碱能神经调节在视觉工作记忆 (VWM) 中发挥关键作用——在短时间内（最多几分钟）保持相关刺激表征可用于认知过程。尽管关于 VWM 的神经和认知机制如何随保留时间动态变化的证据越来越多，但关于胆碱能效应作为非人类灵长类动物 VWM 延迟期的函数的证据不一。使用延迟匹配对恒河猴 (N = 6) 中的 VWM 任务进行采样，我们旨在根据作为延迟持续时间的函数的性能变化来表征 VWM 维护（跨越从 1 到 76 秒的广泛延迟）。然后，我们研究胆碱能神经调节如何使用毒蕈碱受体拮抗剂东莨菪碱作为暂时性遗忘治疗单独给药，影响 VWM 维持，并与两剂乙酰胆碱酯酶抑制剂多奈哌齐联合使用，多奈哌齐是一种广泛使用的阿尔茨海默氏症药物，可用于逆转东莨菪碱引起的损伤。结果表明东莨菪碱诱导的 VWM 维持损伤是延迟依赖性的，并且特别影响 15-33 秒的时间范围，表明东莨菪碱随着时间的推移会恶化 VWM 的正常衰减。多奈哌齐部分挽救了观察到的东莨菪碱诱导的 VWM 性能损害。这些结果为胆碱能张力增加和毒蕈碱神经调节在维持 VWM 数秒后的作用提供了强有力的行为证据，这与我们目前对毒蕈碱乙酰胆碱受体在 VWM 延迟期间持续神经活动中的作用的认识一致。