Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA, United States.
Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA, United States.
Front Neural Circuits. 2017 Dec 5;11:94. doi: 10.3389/fncir.2017.00094. eCollection 2017.
Acetylcholine and dopamine are neurotransmitters that play multiple important roles in perception and cognition. Pharmacological cholinergic enhancement reduces excitatory receptive field size of neurons in marmoset primary visual cortex and sharpens the spatial tuning of visual perception and visual cortical fMRI responses in humans. Moreover, previous studies show that manipulation of cholinergic or dopaminergic signaling alters the spatial tuning of macaque prefrontal cortical neurons during the delay period of a spatial working memory (SWM) task and can improve SWM performance in macaque monkeys and human subjects. Here, we investigated the effects of systemic cholinergic and dopaminergic enhancement on the precision of SWM, as measured behaviorally in human subjects. Cholinergic transmission was increased by oral administration of 5 mg of the cholinesterase inhibitor donepezil, and dopaminergic signaling was enhanced with 100 mg levodopa/10 mg carbidopa. Each neurotransmitter system was separately investigated in double-blind placebo-controlled studies. On each trial of the SWM task, a square was presented for 150 ms at a random location along an invisible circle with a radius of 12 degrees of visual angle, followed by a 900 ms delay period with no stimulus shown on the screen. Then, the square was presented at new location, displaced in either a clockwise (CW) or counterclockwise (CCW) direction along the circle. Subjects used their memory of the location of the original square to report the direction of displacement. SWM precision was defined as the amount of displacement corresponding to 75% correct performance. We observed no significant effect on SWM precision for either donepezil or levodopa/carbidopa. There was also no significant effect on performance on the SWM task (percent correct across all trials) for either donepezil or levodopa/carbidopa. Thus, despite evidence that acetylcholine and dopamine regulate spatial tuning of individual neurons and can improve performance of SWM tasks, pharmacological enhancement of signaling of these neurotransmitters does not substantially affect a behavioral measure of the precision of SWM in humans.
乙酰胆碱和多巴胺是在感知和认知中发挥多种重要作用的神经递质。药理学上增强胆碱能会减少狨猴初级视觉皮层神经元的兴奋性感受野大小，并锐化视觉感知和视觉皮层 fMRI 反应的空间调谐。此外，先前的研究表明，胆碱能或多巴胺能信号的操纵会改变猕猴前额叶皮层神经元在空间工作记忆 (SWM) 任务的延迟期间的空间调谐，并可以提高猕猴和人类受试者的 SWM 表现。在这里，我们研究了系统增强胆碱能和多巴胺能对 SWM 精度的影响，这是通过人类受试者的行为测量来衡量的。通过口服给予 5 毫克乙酰胆碱酯酶抑制剂多奈哌齐来增加胆碱能传递，并用 100 毫克左旋多巴/10 毫克卡比多巴增强多巴胺能信号。在双盲安慰剂对照研究中分别研究了每个神经递质系统。在 SWM 任务的每次试验中，一个正方形以 150 毫秒的时间出现在一个看不见的圆圈上的随机位置，圆圈的半径为 12 度视角，然后是 900 毫秒的延迟期，屏幕上没有显示任何刺激。然后，正方形以新的位置出现在圆圈上，以顺时针 (CW) 或逆时针 (CCW) 方向位移。受试者使用他们对原始正方形位置的记忆来报告位移的方向。SWM 精度定义为与 75%正确表现相对应的位移量。我们没有观察到多奈哌齐或左旋多巴/卡比多巴对 SWM 精度有显著影响。多奈哌齐或左旋多巴/卡比多巴对 SWM 任务的表现（所有试验的正确百分比）也没有显著影响。因此，尽管有证据表明乙酰胆碱和多巴胺调节单个神经元的空间调谐，并可以提高 SWM 任务的表现，但这些神经递质信号的药理学增强并没有显著影响人类 SWM 精度的行为测量。
