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The Journal of Neuroscience, July 1, 2002, 22(13):5760-5768

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 distinct 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 sequences. When the sequences were presented in rapid alternation, damage to the hippocampus, produced either by infusions of the neurotoxin ibotenic acid or by radiofrequency current, produced a severe deficit, although animals with radiofrequency 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

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^* K.L.A. and N.J.F. contributed equally to this work.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22135760-09$05.00/0

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