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agster_fortin2002 - The Journal of Neuroscience July 1 2002...

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The Hippocampus and Disambiguation of Overlapping Sequences Kara L. Agster,* Norbert J. Fortin,* and Howard Eichenbaum Laboratory of Cognitive Neurobiology, Department of Psychology, Boston University, Boston, Massachusetts 02215 Recent models of hippocampal function emphasize its potential role in disambiguating sequences of events that compose dis- tinct episodic memories. In this study, rats were trained to distinguish two overlapping sequences of odor choices. The capacity to disambiguate the sequences was measured by the critical odor choice after the overlapping elements of the se- quences. When the sequences were presented in rapid alter- nation, damage to the hippocampus, produced either by infu- sions of the neurotoxin ibotenic acid or by radiofrequency current, produced a severe deficit, although animals with radio- frequency lesions relearned the task. When the sequences were presented spaced apart and in random order, animals with radiofrequency hippocampal lesions could perform the task. However, they failed when a memory delay was imposed before the critical choice. These findings support the hypothesis that the hippocampus is involved in representing sequences of nonspatial events, particularly when interference between the sequences is high or when animals must remember across a substantial delay preceding items in a current sequence. Key words: rat; hippocampus; sequence memory; sequence disambiguation; episodic memory; olfactory learning; ibotenic acid; radiofrequency In humans, the hippocampus is critical to episodic memory, the ability to recall unique personal experiences (Vargha-Khadem et al., 1997). To address whether this function of the hippocampus extends to animals, recent theoretical considerations have focused on the unique temporal, spatial, and contextual components of episodic memories (Gaffan, 1994; Mishkin et al., 1997; Clayton and Dickinson, 1998). Recent computational models have specif- ically emphasized the potential role of hippocampal circuitry in representing sequences of events that compose the spatial and temporal context of an episode (Levy, 1996; Sohal and Hasselmo, 1998; Wallenstein et al., 1998; Eichenbaum et al., 1999; Lisman, 1999). There is evidence that the hippocampus is important for encoding and retrieving sequential information contained in a unique series of spatial (Kesner and Novak, 1982; Chiba et al., 1994) and nonspatial (Fortin et al., 2002) events. In addition, Levy (1996) proposed that sequence coding by the hippocampus may be especially important when the sequences have overlap- ping elements through which memory of earlier elements must be remembered to complete each distinct sequence. Sohal and Has- selmo (1998) also modeled the overlapping sequence problem and showed how the dynamics of physiological parameters re- flected by the theta rhythm could enhance sequence disambigu- ation by allowing weak associations that match the target se- quence win out during retrieval.
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