This project will examine how neuronal ensembles within the hippocampus, as well as associated parahippocampal cortical areas and prefrontal cortex, represent information in the service of episodic memory for non-spatial information. Our experiments are guided by the hypothesis that information about individual items and spatial context are separately represented in distinct parahippocampal areas, that area CAS encodes items in the context in which they were experienced, and that area CA1 encodes and retrieves the order in which the items were experienced;and our experiments are guided by Hasselmo's models of the mechanisms underlying this scheme. Multi-channel microelectrodes will be used to record the firing patterns of neurons in hippocampal, parahippocampal, and prefrontal areas in rats performing hippocampaldependent tasks that assess rats'ability to remember once-presented sequences of odors and to disambiguate overlapping odor sequences. In the sequence memory paradigm, we will characterize and localize sequence coding, spatial context coding, and coding of item familiarity within this brain system. In the sequence disambiguation paradigm, we will test the hypothesis that overlapping events in two sequences are represented distinctly for each sequence. In both paradigms, we will determine whether there are specific phases of the theta rhythm on which encoding and retrieval of sequence information occur, and whether sequential information from recent experiences persists during a memory delay. For all of these measures we will characterize the extent to which neural firing patterns predict memory performance. The design and focus of these studies is guided by observations of humans performing similar tasks and provides a cellular level analysis not possible in functional imaging studies on humans. These experiments proposed here will be compared with parallel studies on spatial sequence processing, seeking to identify common fundamental mechanisms of non-spatial and spatial sequence representation. The experiments are aimed to test models and to guide the further development of models of hippocampal circuitry that support the temporal organization of episodic memory.

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National Institute of Mental Health (NIMH)
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Boston University
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Kraus, Benjamin J; Brandon, Mark P; Robinson 2nd, Robert J et al. (2015) During Running in Place, Grid Cells Integrate Elapsed Time and Distance Run. Neuron 88:578-89
Brown, Thackery I; Hasselmo, Michael E; Stern, Chantal E (2014) A high-resolution study of hippocampal and medial temporal lobe correlates of spatial context and prospective overlapping route memory. Hippocampus 24:819-39
Prerau, Michael J; Lipton, Paul A; Eichenbaum, Howard B et al. (2014) Characterizing context-dependent differential firing activity in the hippocampus and entorhinal cortex. Hippocampus 24:476-92
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Ross, Robert S; LoPresti, Matthew L; Schon, Karin et al. (2013) Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory. Cogn Affect Behav Neurosci 13:900-15
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Lepage, Kyle Q; Macdonald, Christopher J; Eichenbaum, Howard et al. (2012) The statistical analysis of partially confounded covariates important to neural spiking. J Neurosci Methods 205:295-304

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