Role of NMDA in the Visual Working Memory of the Macaque Monkey

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Heijselaar, Evelien Suzanne
working memory , NMDA
Working memory refers to the ability to retain information for short periods of time to guide future behavior. This type of short-term memory has been shown to play an important role in mental disorders such as schizophrenia and therefore further investigations into the neural basis of this cognitive function may aid in the study of disease states where this cognitive function is defective. A likely neural correlate of working memory has been identified in the persistent neural activity observed during the memory retention intervals of various behavioral tasks. Computational and cellular physiology has suggested that this persistent activity depends on NMDA receptor activation. Indeed, pharmacological studies on both human and animal subjects have reported a significant decrease in working memory task performance following the administration of NMDA-antagonists such as ketamine. However, the task and experimental design of these previous studies have not been ideal, and have therefore only shown equivocal evidence that NMDA-antagonists impair working memory, especially its capacity. Here we aimed to determine the effect of low-dose ketamine injection (0.25-mg/kg and 0.50-mg/kg IM) on the performance of macaque monkeys on a visual sequential comparison task, a task whose performance has minimal influence from other cognitive functions besides working memory. All monkeys showed a detrimental effect of ketamine administration on visual working memory performance, either at higher ketamine doses or with high memory loads. There was also an effect on performance in sessions without a memory component, indicating that the effect of ketamine was no limited to working memory maintenance. Although the effect of ketamine on memory load varied per animal, this study provides solid evidence in support of the hypothesis that working memory maintenance is dependent on NMDA receptor integrity.
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