Hippocampal ensemble dynamics during active ambulation, passive movement & rest

描述(申请人提供)：在静态条件下，灵长类动物内侧颞叶的细胞已被证明选择性地向物体或猴子面前物体的位置发射(Rolls等人，1989；里奇斯等人，1991)。然而，在检查了运动条件后，发现海马体的活动受到环境中特定的视觉刺激、环境中的位置、与任务相关的线索或这些因素的组合的影响(Ono等人，1991；1993)。此外，已经观察到灵长类海马体内的一些神经元与空间中某一位置的特定凝视方向有关的放电(“空间视角”；O‘Mara&Rolls，1995)。Wirth和他的同事(2003)观察到，在获得新的位置-刺激联系的过程中，部分神经元根据行为表现改变了它们的活动，这表明了一种可以长期储存记忆的机制。尽管海马体在记忆编码和巩固中的作用几乎是毋庸置疑的，但目前尚不清楚灵长类海马体中的单个细胞是优先受到感觉刺激的驱动，还是在自由运动中表现出完全不同的相关性。直到最近，由于技术限制，才有可能直接检验这一假说。我们在Neuralynx，Inc.的长期合作伙伴的发展已经提供了通过使用遥测记录来调查这一问题的手段。此外，该系统的电池容量可以记录长达6个小时的数据，使数据能够在行为时期以及睡眠和安静清醒期间收集。尽管在灵长类动物的几个大脑皮层区域已经记录到在这些“离线”期间的活动模式重新激活(Hoffman和McNaughton，2002)，但在海马区还没有进行直接记录。由于最近发现波纹/尖锐波事件发生在组织学证实的非人灵长类动物的海马区(Skaggs等人，2007年)，因此有理由假设在行为过程中观察到的神经活动模式将在这些尖锐波时期重新激活(Kudrimoti等人，1999年)。这项建议的目标可以总结为以下两个目的：1)确定与动物被动移动到同一环境中的不同奖励位置相比，当动物穿梭于食物奖励时，主动和被动运动是否影响海马神经元的放电关联；2)研究在行为过程中活跃的神经群是否在尖波/涟漪时期重新激活。这些研究将为灵长类动物在自然行为中的海马单单位活动和脑电提供明确的分类，并将为睡眠和清醒状态下海马体活动模式的相关性提供重要的见解。

DESCRIPTION (provided by applicant): Under static conditions, cells in the primate medial temporal lobe have been shown to selectively fire to objects or the location of objects in front of the monkey (Rolls et al., 1989; Riches et al., 1991). After examining conditions of movement, however, hippocampal activity was found to be affected by specific visual stimuli in an environment, places within an environment, task-related cues, or a combination of these (Ono et al., 1991; 1993). Additionally, some neurons within the primate hippocampus have been observed to fire in relation to the specific direction of gaze towards a location in space ("spatial view"; O'Mara & Rolls, 1995). Wirth and colleagues (2003) observed that during the acquisition of new place-stimuli associations, a portion of neurons altered their activity based on the behavioral performance, suggesting a mechanism by which memories could be stored long-term. Although the role of the hippocampus in memory encoding and consolidation is virtually undisputed, it is not known whether single cells in the primate hippocampus are preferentially driven by sensory stimuli, or exhibit entirely different correlates during unrestrained movement. It has not been possible to test this hypothesis directly until recently due to technological limitations. Developments by our long-time collaborators at Neuralynx, Inc. have provided the means to investigate this issue through the use of telemetric recordings. Moreover, the system has the battery capacity to record for up to 6 hours, enabling data to be collected during behavioral epochs as well as during periods of sleep and quiet-wakefulness. Although activity pattern reactivation during these 'off-line' periods has been documented in several cortical regions of the primate (Hoffman and McNaughton, 2002), direct recordings within the hippocampus have not yet been performed. Because ripple/sharp-wave events have recently been found to occur in histologically-verified hippocampal regions of the nonhuman primate (Skaggs et al., 2007), it is reasonable to hypothesize that neural activity patterns observed during behavior will be reactivated during these periods of sharp waves (Kudrimoti et al., 1999). The goals of this proposal can be summarized in the following two aims: 1) to determine whether active versus passive movement affects the firing correlates of hippocampal neurons when the animal is shuttling for food reward compared to the condition where the animal is passively moved to between reward locations within the same environment, and 2) to examine whether neural ensembles active during behavior are reactivated during sharp-wave/ripple epochs. These studies will provide definitive classifications of hippocampal single unit activity and EEG in the primate during naturalistic behaviors and will provide significant insights into the correlates of hippocampal activity patterns during sleep and waking states.