Impaired memory is an important component of diseases such as Alzheimer's disease, temporal lobe epilepsy, depression, and schizophrenia that collectively affect over twenty million Americans. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes, in order to bring us closer to developing new therapies for these disabled patients. While it has long been recognized that medial temporal lobe structures are important for mnemonic processing, studies in rodents have also identified exquisite spatial representations in these regions in the form of place cells in the hippocampus and grid and border cells in the entorhinal cortex. A recent area of investigation has focused on understanding the generation of these spatial representations, for which theta-band activity has been hypothesized to play a major role. However, very little is known about whether neurons in the primate hippocampal formation demonstrate theta-band rhythmic activity and almost nothing is known about potentially analogous spatial representations in the primate hippocampus and entorhinal cortex. The lack of understanding in this area inhibits our ability to link the large body of previous findings from rodents to humans and prevents a full understanding of the function of these structures. Based on preliminary data, we hypothesize that neural activity in the primate hippocampus and entorhinal cortex reflects an allocentric spatial coordinate frame, during both 2-D visuospatial exploration and 3-D virtual navigation. The experiments proposed here will directly test this hypothesis, using multi-electrode recordings of spiking activity and the local field potential (LFP) in the hippocampus and entorhinal cortex of rhesus monkeys engaged in free-viewing memory tasks and virtual navigation. We will examine modulations in single-unit firing rates, LFP power, and spike-field neuronal synchronization with respect to eye fixation location, saccade direction, heading direction, location in virtual space, and memory performance. Recordings will be carried out throughout these structures in order to identify the anatomical distribution of particular representations. The proposed experiments have the following potential outcomes: 1) to demonstrate whether the structure of the spatial code in the primate hippocampal formation is universal across stimulus domains, i.e., virtual 3-D and visual space, 2) to inform models that describe the generation of these spatial responses by identifying the extent to which these representations are related to network oscillatory activity, and 3) to identify the extent to which neural activity in the hippocampal formation is modulated by visuospatial and environmental exploration and how this modulation impacts memory formation.

Public Health Relevance

Impaired memory is an important component of diseases such as temporal lobe epilepsy, depression, schizophrenia, and Alzheimer's disease that collectively affect over twenty million Americans. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes, in order to bring us closer to developing new therapies for these disabled patients. The objective of this proposal is to characterize spatial and visual object representations in the primate hippocampus and entorhinal cortex. This knowledge will allow us to better understand the function of these structures in primates and may bring us closer to developing new therapies for memory- impaired populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH080007-06A1
Application #
8632095
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2007-04-01
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
6
Fiscal Year
2014
Total Cost
$505,611
Indirect Cost
$221,560
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Jutras, Michael J; Buffalo, Elizabeth A (2014) Oscillatory correlates of memory in non-human primates. Neuroimage 85 Pt 2:694-701
K├Ânig, Seth D; Buffalo, Elizabeth A (2014) A nonparametric method for detecting fixations and saccades using cluster analysis: removing the need for arbitrary thresholds. J Neurosci Methods 227:121-31
Solyst, James A; Buffalo, Elizabeth A (2014) Social relevance drives viewing behavior independent of low-level salience in rhesus macaques. Front Neurosci 8:354
Vinck, Martin; Womelsdorf, Thilo; Buffalo, Elizabeth A et al. (2013) Attentional modulation of cell-class-specific gamma-band synchronization in awake monkey area v4. Neuron 80:1077-89
Jutras, Michael J; Fries, Pascal; Buffalo, Elizabeth A (2013) Oscillatory activity in the monkey hippocampus during visual exploration and memory formation. Proc Natl Acad Sci U S A 110:13144-9
Jutras, Michael J; Buffalo, Elizabeth A (2010) Recognition memory signals in the macaque hippocampus. Proc Natl Acad Sci U S A 107:401-6
Jutras, Michael J; Fries, Pascal; Buffalo, Elizabeth A (2009) Gamma-band synchronization in the macaque hippocampus and memory formation. J Neurosci 29:12521-31