Hippocampal ensemble dynamics during active ambulation, passive movement & rest

描述（由申请人提供）：在静态条件下，灵长类动物内侧颞叶的细胞被证明有选择性地向猴子面前的物体或物体的位置发射信号（Rolls et al., 1989; rich et al., 1991）。然而，在检查了运动条件后，发现海马体活动受到环境中特定视觉刺激、环境中的地点、任务相关线索或这些因素的组合的影响（Ono et al., 1991; 1993）。此外，灵长类动物海马体中的一些神经元被观察到与凝视空间中某个位置的特定方向有关（“空间视图”；O’mara & Rolls, 1995）。Wirth和他的同事（2003）观察到，在获得新的地点刺激关联的过程中，一部分神经元根据行为表现改变了它们的活动，这表明了一种记忆可以长期储存的机制。尽管海马体在记忆编码和巩固中的作用几乎是无可争议的，但尚不清楚灵长类动物海马体中的单个细胞是否优先受到感觉刺激的驱动，或者在不受约束的运动中表现出完全不同的相关性。由于技术限制，直到最近才有可能直接验证这一假设。我们在Neuralynx， Inc.的长期合作伙伴的发展，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以记录长达6小时的数据，从而可以在行为时期、睡眠和清醒时期收集数据。虽然在这些“离线”时期的活动模式再激活已经在灵长类动物的几个皮质区域被记录下来（Hoffman和McNaughton， 2002），但在海马体内部的直接记录尚未被执行。由于波纹/锐波事件最近被发现发生在经组织学验证的非人类灵长类动物的海马区域（Skaggs等，2007），因此有理由假设，在行为期间观察到的神经活动模式将在这些锐波期间被重新激活（Kudrimoti等，1999）。本研究的目标可以概括为以下两个目的：1)确定主动与被动运动是否会影响海马神经元的放电相关，当动物在食物奖励中穿梭时，与动物在同一环境中被动地在奖励位置之间移动的情况相比；2)检查在行为期间活跃的神经系统是否在尖峰波/涟漪时期被重新激活。这些研究将提供灵长类动物在自然行为时海马单单位活动和脑电图的明确分类，并将对睡眠和清醒状态下海马活动模式的相关性提供重要见解。

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.