title: Novelty and anxiolytic drugs dissociate two components of hippocampal theta in behaving rats.
abstract: 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.
authors.affiliation: Institute of Psychological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wells
authors.forename: Doran P
authors.initials: DP
authors.lastname: Amos
authors.forename: Ali
authors.initials: A
authors.lastname: Jeewajee
authors.forename: Vincent
authors.initials: V
authors.lastname: Douchamps
authors.forename: John
authors.initials: J
authors.lastname: Rodgers
authors.forename: John
authors.initials: J
authors.lastname: O'Keefe
authors.forename: Neil
authors.initials: N
authors.lastname: Burgess
authors.forename: Colin
authors.initials: C
authors.lastname: Lever
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents