The hippocampus plays a critical role in the formation of new memories; however, it is not clear how information is structured and processed by the hippocampal network in the service of memory formation. The microcircuitry of the hippocampus is richly interconnected, which produces robust, temporally-structured activity spanning ensembles of neurons. Microcircuit motifs resonate at characteristic frequencies when they become active, recruiting hippocampal neurons into coordinated circuits that can be detected in the rhythmicity of local field potentials (LFP). The hippocampal LFP in primates demonstrates a complex mixture of oscillatory signatures, and there is often no dominant frequency in the signal during memory tasks. This stands in stark contrast to the prominent theta band (6-10 Hz) oscillation that occurs in rodents selectively during exploration and task performance as the animal actively processes incoming information. Theta-rhythmic activity in the rodent hippocampus is coordinated by input from the medial septum, which is a connectional pathway that is conserved across all mammals. Although monkeys lack this sustained archetypal theta-band activity in the LFP, the preservation of anatomy across species suggests the presence of a circuit that would similarly govern hippocampal information processing in primates. In this proposal, we will combine newly available electrophysiological technology with innovative computational approaches to quantify and model complex signals of the primate LFP. Single-unit and LFP activity will be simultaneously recorded from the full extent of the hippocampus using chronically-implanted hyperdrives and linear electrode arrays while monkeys perform a spatial memory task in virtual reality. In addition, we will examine the effects of medial septum stimulation on hippocampal oscillatory dynamics and behavior. We will take advantage of novel spectral analysis techniques to improve interpretation of LFPs characterized by transient and irregular oscillations. The proposed experiments have the following potential outcomes: 1) to determine the relationship of hippocampal oscillatory states to neuronal spiking and memory task events, 2) to develop data-driven computational models that characterize patterns in hippocampal oscillations as they unfold in time and across hippocampal subfields during memory task events, and 3) to identify the extent to which the medial septum drives oscillatory activity mediating active processing in the hippocampus.

Public Health Relevance

A large body of research in rodents has identified prominent hippocampal rhythms, such as the theta band (6-10 Hz) oscillation, which occur in conjunction with exploration and memory task performance; however, there is a surprising gap in our understanding regarding oscillatory activity in the primate hippocampus. Here, we propose to take advantage of newly available large-scale recording techniques along with targeted electrical stimulation and innovative data-driven modeling approaches to characterize synchronized network states and their behavioral correlates in the primate. These efforts will allow us to identify hallmarks of attentive processing in the healthy hippocampus, and have the potential to advance our understanding of the possible therapeutic effects of targeted neural stimulation for memory enhancement.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Buhring, Bettina D
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University of Washington
Schools of Medicine
United States
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