Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 5C1, Canada.
J Neurosci. 2012 Aug 29;32(35):12018-27. doi: 10.1523/JNEUROSCI.1510-12.2012.
Ketamine, an NMDA receptor antagonist, has been shown to induce behavioral abnormalities in humans that mimic the positive, negative, and most importantly cognitive deficits observed in schizophrenia. Similar cognitive deficits have been observed in nonhuman primates after a subanesthetic dose of ketamine, including an impairment in their ability to perform the antisaccade task, which requires the suppression of a prosaccade toward a flashed stimulus and the generation of a saccade in the opposite direction. The neural basis underlying these cognitive impairments remains unknown. Here, we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine during the performance of randomly interleaved prosaccade and antisaccade trials. Ketamine impeded the monkeys' ability to maintain and apply the correct task rule and increased reaction times of prosaccades and antisaccades. These behavioral changes were associated with an overall increase in activity of PFC neurons and a reduction in their task selectivity. Our results suggest that the mechanism underlying ketamine-induced cognitive abnormalities may be the nonspecific increase in PFC activity and the associated reduction of task selectivity.
氯胺酮是一种 NMDA 受体拮抗剂，已被证明可在人类中诱导出类似于精神分裂症中观察到的阳性、阴性和最重要的认知缺陷的行为异常。在亚麻醉剂量的氯胺酮后，非人类灵长类动物也观察到类似的认知缺陷，包括它们执行反扫视任务的能力受损，该任务需要抑制对闪烁刺激的扫视，并在相反方向产生扫视。这些认知缺陷的神经基础仍不清楚。在这里，我们在猴子执行随机交错的扫视和反扫视试验期间，在亚麻醉剂量的氯胺酮给药前后记录了外侧前额叶皮层的单个神经元活动。氯胺酮阻碍了猴子维持和应用正确任务规则的能力，并增加了扫视和反扫视的反应时间。这些行为变化与 PFC 神经元活动的整体增加和它们的任务选择性降低有关。我们的结果表明，氯胺酮引起的认知异常的机制可能是 PFC 活动的非特异性增加和相关的任务选择性降低。
