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.
The outcome of the proposed project will have a significant impact on our understanding of the neural basis of episodic memory and how the hippocampus, a prominent structure in the brain, supports this cognitive process. A more comprehensive understanding of hippocampal function is a prerequisite for successful development of therapeutic or preventative treatments for neurological disorders that selectively impact this structure, such as Alzheimer's disease. Moreover, these data will provide new approaches to studying, and ultimately ameliorating, memory disorders arising from other sources such as aging, stress, drug abuse, and brain trauma.
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