Nowhere is the significance of neural plasticity more evident than in amnesic patients with damage to the medial temporal lobe. These patients exhibit a profound, selective and long-lasting inability to form or retain new long-term memory for facts and events, termed declarative memory in humans and relational memory in animals. One prototypical form of declarative/relational memory is memory for spatial information. The goal of this proposal is to define the patterns of neural activity that underlie 2 important aspects of memory for spatial information in the macaque monkey hippocampus and entorhinal cortex. First, our preliminary data show that hippocampal and cortical neurons signal learning of new spatial associations (object-place association task) with dramatic changes in neural activity termed """"""""changing cells"""""""".
Specific Aim 1 will define which aspect/s of the learned object-place association control/s the changing cells. These studies will determine how error trials and systematic manipulations of object identity, place specificity, motor response and behavioral context control the activity of the changing cells. A second key aspect of spatial memory for trajectories or journeys (i.e., how to get from point A to point B) is the ability to remember the temporal order of events in a spatial sequence.
Specific Aim 2 will examine both the long-term and working memory signals in the hippocampus and entorhinal cortex during the performance of a delayed sequence recall task where animals must reproduce the order of three-item sequences from memory.
Specific Aim 3 will further categorize the task-related and memory-related cells identified in the hippocampus and entorhinal cortex in Specific Aims 1 and 2 into either putative excitatory (PE) or fast spiking (FS) cells. These experiments will also attempt to identify clear theta activity in the monkey hippocampus and superficial entorhinal cortex. Thus, these latter experiments will allow us to 1) link cells with particular task-related or mnemonic signals to specific cell types (i.e., PE or FS cells) and phases of theta and 2) compare the relationship between cell type/theta modulation and neural response observed in monkeys to that described in rats. The results from these studies have implications for understanding a variety of neurological states associated with memory dysfunction including Alzheimer's disease, epilepsy and schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH058847-06
Application #
6822987
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (03))
Program Officer
Anderson, Kathleen C
Project Start
1999-07-01
Project End
2009-04-30
Budget Start
2004-07-02
Budget End
2005-04-30
Support Year
6
Fiscal Year
2004
Total Cost
$303,624
Indirect Cost
Name
New York University
Department
Neurology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Sakon, John J; Naya, Yuji; Wirth, Sylvia et al. (2014) Context-dependent incremental timing cells in the primate hippocampus. Proc Natl Acad Sci U S A 111:18351-6
Hargreaves, Eric L; Mattfeld, Aaron T; Stark, Craig E L et al. (2012) Conserved fMRI and LFP signals during new associative learning in the human and macaque monkey medial temporal lobe. Neuron 74:743-52
Naya, Yuji; Suzuki, Wendy A (2011) Integrating what and when across the primate medial temporal lobe. Science 333:773-6
Sarma, Sridevi V; Nguyen, David P; Czanner, Gabriela et al. (2011) Computing confidence intervals for point process models. Neural Comput 23:2731-45
Smith, Anne C; Scalon, Joao D; Wirth, Sylvia et al. (2010) State-space algorithms for estimating spike rate functions. Comput Intell Neurosci :426539
Wirth, Sylvia; Avsar, Emin; Chiu, Cindy C et al. (2009) Trial outcome and associative learning signals in the monkey hippocampus. Neuron 61:930-40
Yanike, Marianna; Wirth, Sylvia; Smith, Anne C et al. (2009) Comparison of associative learning-related signals in the macaque perirhinal cortex and hippocampus. Cereb Cortex 19:1064-78
Prerau, M J; Smith, A C; Eden, U T et al. (2008) A mixed filter algorithm for cognitive state estimation from simultaneously recorded continuous and binary measures of performance. Biol Cybern 99:1-14
Suzuki, Wendy A (2008) Associative learning signals in the brain. Prog Brain Res 169:305-20
Czanner, Gabriela; Eden, Uri T; Wirth, Sylvia et al. (2008) Analysis of between-trial and within-trial neural spiking dynamics. J Neurophysiol 99:2672-93

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