Hippocampal ensemble dynamics during active ambulation, passive movement & rest

描述（由申请人提供）：在静态条件下，灵长类内侧颞叶中的细胞已经显示出选择性地向猴子前方的物体或物体的位置发射（Rolls等人，1989; Riches等人，1991年）。然而，在检查运动条件后，发现海马活动受到环境中的特定视觉刺激、环境内的位置、任务相关线索或这些的组合的影响（Ono等人，1991; 1993）。此外，已经观察到灵长类动物海马体内的一些神经元与朝向空间中的位置的特定凝视方向有关（“空间视图”; O 'Mara & Rolls，1995）。Wirth及其同事（2003）观察到，在获得新的位置刺激关联的过程中，一部分神经元根据行为表现改变了它们的活动，这表明记忆可以长期存储的机制。虽然海马体在记忆编码和巩固中的作用几乎是无可争议的，但我们不知道灵长类海马体中的单个细胞是否优先受到感官刺激的驱动，或者在无限制的运动中表现出完全不同的相关性。由于技术上的限制，直到最近才能直接检验这一假设。由我们在Neuralynx，Inc.的长期合作伙伴开发。通过使用遥测记录，提供了调查这一问题的手段。此外，该系统的电池容量可记录长达6小时，使数据能够在行为时期以及睡眠和安静清醒期间收集。虽然在灵长类动物的几个皮层区域中已经记录了这些“离线”期间的活动模式再激活（霍夫曼和McNaughton，2002年），但尚未进行海马体内的直接记录。因为最近已经发现涟漪/尖波事件发生在非人灵长类动物的组织学验证的海马区域中（Skaggs等人，2007），合理地假设在行为期间观察到的神经活动模式将在这些尖波期间被重新激活（Kudrimoti等人，1999年）。该提案的目标可归纳为以下两个目标：1）确定与动物被动地移动到相同环境内的奖励位置之间的条件相比，当动物为食物奖励而穿梭时主动与被动移动是否影响海马神经元的放电相关性，以及2）检查在行为期间活跃的神经系综是否在尖波/涟漪时期期间被重新激活。这些研究将提供明确的分类海马单单位活动和EEG在灵长类动物在自然行为，并将提供显着的洞察海马活动模式的相关性在睡眠和清醒状态。

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.