HIPPOCAMPAL CONTROL OF WORKING MEMORY: INACTIVATION AND PET IN MONKEYS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 本项目探索非人灵长类动物工作记忆过程中海马背外侧前额叶皮质(DlPFC)的控制。我们正在使用可逆失活技术，结合行为测试和PET成像来测试这一假设，即在非人类灵长类动物中，海马体通过中脑边缘多巴胺系统(包括伏隔核、腹侧苍白球和腹侧被盖区(VTA)的回路)调节背侧PFC功能。具体地说，我们测试了腹侧苍白球功能强直地抑制VTA神经元，直到被海马诱发的伏隔核释放所抑制的假设。我们目前正在对第一组实验中的3只猴子进行测试。受试者已经接受了训练和植入，我们正在比较在视觉配对比较任务(VPC)中对猴子进行视觉配对比较任务(VPC)时，向海马区注射麝香酚和生理盐水的效果。行为测试之后是在蝇油或生理盐水下进行正电子发射计算机断层扫描。去年购买的第二套动物已经完成了第一个疗程的训练，即将植入。然后，他们将被用来评估中脑边缘多巴胺系统作为海马体和dlPFC之间的中介的作用。我们将使用GABA-A拮抗剂荷包牡丹碱来调节伏隔核的活动，其最终结果是减少向dlPFC释放多巴胺，从而损害工作记忆。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project explores hippocampal control of dorsolateral prefrontal cortex (dlPFC) during working memory performance in nonhuman primates. We are using reversible inactivation techniques in combination with behavioral testing and PET imaging to test the hypothesis that the hippocampus modulates dorsolateral PFC function via the meso-limbic dopamine system (a circuit including the nucleus accumbens, ventral pallidum and ventral tegmental area (VTA)) in nonhuman primates. Specifically, we test the hypothesis that the ventral pallidum functions to tonically inhibit VTA neurons until inhibited by hippocampal evoked release from the nucleus accumbens. We are currently testing the 3 monkeys in the first set of experiments. The subjects have been trained and implanted and we are comparing the effects of muscimol vs. saline injections into the hippocampus while the monkeys are tested on the visual paired comparison task (VPC). Behavioral testing is followed by PET scanning under muscimol or saline. The second set of animals purchased last year has completed the first course of training and are about to be implanted. They will then be used to assess the role of the meso-limbic dopamine system as the intermediary between the hippocampus and dlPFC. We will modulate activity of the nucleus accumbens using the GABA-A antagonist bicuculline, the net result of which is to reduce dopamine release into the dlPFC, impairing working memory.