Novelty and anxiolytic drugs dissociate two components of hippocampal theta in behaving rats

Christine E Wells, Doran P Amos, Ali Jeewajee, Vincent Douchamps, John Rodgers, John O'Keefe, Neil Burgess, Colin Lever

    Research output: Contribution to journalArticlepeer-review

    67 Citations (Scopus)
    279 Downloads (Pure)


    Hippocampal processing is strongly implicated in both spatial cognition and anxiety and is temporally organized by the theta rhythm. However, there has been little attempt to understand how each type of processing relates to the other in behaving animals, despite their common substrate. In freely moving rats, there is a broadly linear relationship between hippocampal theta frequency and running speed over the normal range of speeds used during foraging. A recent model predicts that spatial-translation-related and arousal/anxiety-related mechanisms of hippocampal theta generation underlie dissociable aspects of the theta frequency-running speed relationship (the slope and intercept, respectively). Here we provide the first confirmatory evidence: environmental novelty decreases slope, whereas anxiolytic drugs reduce intercept. Variation in slope predicted changes in spatial representation by CA1 place cells and novelty-responsive behavior. Variation in intercept predicted anxiety-like behavior. Our findings isolate and doubly dissociate two components of theta generation that operate in parallel in behaving animals and link them to anxiolytic drug action, novelty, and the metric for self-motion.

    Original languageEnglish
    Pages (from-to)8650-67
    Number of pages18
    JournalJournal of Neuroscience
    Issue number20
    Publication statusPublished - 15 May 2013


    • Analysis of Variance
    • Animals
    • Anti-Anxiety Agents
    • Anxiety
    • Body Temperature
    • Disease Models, Animal
    • Dose-Response Relationship, Drug
    • Electroencephalography
    • Evoked Potentials
    • Exploratory Behavior
    • Hippocampus
    • Male
    • Rats
    • Space Perception
    • Theta Rhythm
    • Time Factors
    • Wakefulness
    • Journal Article
    • Research Support, Non-U.S. Gov't


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