Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys.
Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys.
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DOI：
10.1016/j.cub.2017.07.021
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发表时间：
2017-09-11
期刊：
影响因子：
--
通讯作者：
Blake DT
中科院分区：
文献类型：
--
作者：
Liu R;Crawford J;Callahan PM;Terry AV Jr;Constantinidis C;Blake DT
新皮层中的乙酰胆碱对执行功能至关重要。衰老和阿尔茨海默氏痴呆中胆碱能神经元的变性通常用胆碱酯酶抑制剂治疗，然而，这些抑制剂是适度有效的并且与副作用相关，这妨碍了许多患者的有效剂量。电激活Meynert基底核（NB），新皮质乙酰胆碱的来源，提供了一种潜在的方法，改善胆碱能激活。在这里，我们测试了NB刺激是否会改善非人类灵长类动物模型中工作记忆任务的表现。出乎意料的是，间歇性刺激被证明是最有益的（每秒60个脉冲，每分钟20秒），而连续刺激往往损害性能。药理学实验证实，其作用依赖于胆碱能激活。多奈哌齐，胆碱酯酶抑制剂，恢复连续刺激受损的动物的性能，但在间歇性刺激期间没有进一步改善性能。烟碱或毒蕈碱受体拮抗剂使间歇性刺激无效。在刺激开始后的几个月里，在没有刺激的情况下，表现也有所改善。我们的研究结果表明，间歇性NB刺激可以改善工作记忆，这一发现对恢复衰老和阿尔茨海默氏痴呆症的认知功能具有重要意义。
Acetylcholine in the neocortex is critical for executive function. Degeneration of cholinergic neurons in aging and Alzheimer’s Dementia is commonly treated with cholinesterase inhibitors, however, these are modestly effective and are associated with side-effects, which preclude effective dosing in many patients. Electrical activation of the Nucleus Basalis (NB) of Meynert, the source of neocortical acetylcholine provides a potential method of improving cholinergic activation. Here we tested whether NB stimulation would improve performance of a working memory task in a non-human primate model. Unexpectedly, intermittent stimulation proved to be most beneficial (60 pulses per second, for 20 seconds every minute), whereas continuous stimulation often impaired performance. Pharmacological experiments confirmed that the effects depended on cholinergic activation. Donepezil, a cholinesterase inhibitor, restored performance in animals impaired by continuous stimulation but did not improve performance further during intermittent stimulation. Intermittent stimulation was rendered ineffective by either nicotinic or muscarinic receptor antagonists. In the months after stimulation began, performance also improved in sessions without stimulation. Our results reveal that intermittent NB stimulation can improve working memory, a finding that has implications for restoring cognitive function in aging and Alzheimer’s Dementia.
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