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The first insights into the neuronal and neurotransmitter basis of working memory came from animal research. The work of Jacobsen and Fulton in the 1930s first showed that lesions to the PFC impaired spatial working memory performance in monkeys. The later work of Joaquin Fuster recorded the electrical activity of neurons in the PFC of monkeys while they were doing a delayed matching task. In that task, the monkey sees how the experimenter places a bit of food under one of two identical-looking cups. A shutter is then lowered for a variable delay period, screening off the cups from the monkey's view. After the delay, the shutter opens and the monkey is allowed to retrieve the food from under the cups. Successful retrieval in the first attempt – something the animal can achieve after some training on the task – requires holding the location of the food in memory over the delay period. Fuster found neurons in the PFC that fired mostly during the delay period, suggesting that they were involved in representing the food location while it was invisible. Later research has shown similar delay-active neurons also in the posterior parietal cortex, the thalamus, the caudate, and the globus pallidus. The work of Goldman-Rakic and others showed that principal sulcal, dorsolateral PFC interconnects with all of these brain regions, and that neuronal microcircuits within PFC are able to maintain information in working memory through recurrent excitatory glutamate networks of pyramidal cells that continue to fire throughout the delay period. These circuits are tuned by lateral inhibition from GABAergic interneurons. The neuromodulatory arousal systems markedly alter PFC working memory function; for example, either too little or too much dopamine or norepinephrine impairs PFC network firing and working memory performance.

The first insights into the neuronal and neurotransmitter basis of working memory came from animal research. The work of Jacobsen and Fulton in the 1930s first showed that lesions to the PFC impaired spatial working memory performance in monkeys. The later work of Joaquin Fuster recorded the electrical activity of neurons in the PFC of monkeys while they were doing a delayed matching task. In that task, the monkey sees how the experimenter places a bit of food under one of two identical-looking cups. A shutter is then lowered for a variable delay period, screening off the cups from the monkey's view. After the delay, the shutter opens and the monkey is allowed to retrieve the food from under the cups. Successful retrieval in the first attempt – something the animal can achieve after some training on the task – requires holding the location of the food in memory over the delay period. Fuster found neurons in the PFC that fired mostly during the delay period, suggesting that they were involved in representing the food location while it was invisible. Later research has shown similar delay-active neurons also in the posterior parietal cortex, the thalamus, the caudate, and the globus pallidus. The work of Goldman-Rakic and others showed that principal sulcal, dorsolateral PFC interconnects with all of these brain regions, and that neuronal microcircuits within PFC are able to maintain information in working memory through recurrent excitatory glutamate networks of pyramidal cells that continue to fire throughout the delay period. These circuits are tuned by lateral inhibition from GABAergic interneurons. The neuromodulatory arousal systems markedly alter PFC working memory function; for example, either too little or too much dopamine or norepinephrine impairs PFC network firing and working memory performance.

对工作记忆的神经元和神经递质基础的第一次见解来自动物研究。雅各布森和富尔顿在20世纪30年代的研究首次表明，对 PFC 的损害损害了猴子的空间工作记忆能力。后来，华金 · 福斯特的工作记录了猴子在完成延迟匹配任务时 PFC 中神经元的电活动。在这个任务中，猴子看到实验者是如何把一点食物放在两个看起来一模一样的杯子下面的。然后，一个快门降低一个可变的延迟时间，屏蔽掉猴子的视线。在延迟之后，快门打开，猴子可以从杯子下面取出食物。在第一次尝试中成功地提取食物——这是动物经过一些训练后能够完成的任务——需要在延迟期内保持食物在记忆中的位置。福斯特发现 PFC 中的神经元在延迟期间大部分被激活，这表明他们参与了食物位置的表现，而食物位置是看不见的。后来的研究表明，后顶叶皮层、丘脑、尾状核和苍白球也有类似的延迟活动神经元。Goldman-Rakic 等人的研究表明，脊髓背外侧的 PFC 与所有这些大脑区域相互连接，PFC 内的神经元微回路能够通过反复兴奋的锥体细胞谷氨酸网络来维持工作记忆中的信息，这些神经元网络在整个延迟期间持续激活。这些回路是由 gaba 能中间神经元的侧抑制调节的。神经调节性唤起系统显著改变 PFC 工作记忆功能; 例如，过多或过少的多巴胺或去甲肾上腺素损害 PFC 神经网络的放电和工作记忆的表现。

关于工作记忆的神经元和神经递质基础的初次见解来自动物研究。雅各布森 Jacobsen 和富尔顿 Fulton在20世纪30年代的研究首次表明猴子的空间工作记忆能力因PFC的损害而减损。华金 · 福斯特 Joaquin Fuster 的后续工作记录了猴子在完成延迟匹配任务时 PFC 中神经元的电活动。在该任务中，猴子看到实验人员在两个同样杯子中的一个下面放了一点食物。然后一个挡板降下挡住猴子对杯子的视线一段时间（延迟变量）。之后挡板打开，允许猴子从杯子下面取出食物。在第一次尝试中它成功地提取食物——系动物经过一些训练后能够完成的任务——要求动物在延迟期维持食物位置的记忆。福斯特发现延迟期间PFC中的大部分神经元激活了，表明这些神经元参与了在看不到食物期间对其位置的记忆维持。后来的研究发现后顶叶皮层、丘脑、尾状核和苍白球也有类似的延迟活动神经元。高德马・拉齐克 Goldman-Rakic 等人的研究表明，脊髓背外侧的PFC与所有这些大脑区域相互连接，PFC内的神经元微回路能够通过反复兴奋的锥体细胞谷氨酸网络来维持工作记忆中的信息，这些神经元网络在整个延迟期间是持续激活的。这些回路是由GABA能中间神经元的侧抑制调节的。神经调节性唤起系统显著改变了PFC工作记忆功能; 例如，过多或过少的多巴胺或去甲肾上腺素会减损PFC神经网络放电和工作记忆表现。