title: The role of the dorsal hippocampus in two versions of the touchscreen automated paired associates learning (PAL) task for mice.
abstract: BACKGROUND
  The CANTAB object-location paired-associate learning (PAL) test can detect cognitive deficits in schizophrenia and Alzheimer's disease. A rodent version of touch screen PAL (dPAL) has been developed, but the underlying neural mechanisms are not fully understood. Although there is evidence that inactivation of the hippocampus following training leads to impairments in rats, this has not been tested in mice. Furthermore, it is not known whether acquisition, as opposed to performance, of the rodent version depends on the hippocampus. This is critical as many mouse models may have hippocampal dysfunction prior to the onset of task training.
  
  
  OBJECTIVE
  The objectives of this study are to examine the effects of dorsal hippocampal (dHp) dysfunction on both performance and acquisition of mouse dPAL and to determine if hippocampal task sensitivity could be increased using a newly developed context-disambiguated PAL (cdPAL) paradigm.
  
  
  METHODS
  In experiment 1, C57Bl/6 mice received post-acquisition dHp infusions of the GABA agonist muscimol. In experiment 2, C57Bl/6 mice received excitotoxic dHp lesions prior to dPAL/cdPAL acquisition.
  
  
  RESULTS
  Post-acquisition muscimol dose-dependently impaired dPAL and cdPAL performance. Pre-acquisition dHp lesions had only mild effects on both PAL tasks. Behavioural challenges including addition of objects and degradation of the visual stimuli with noise did not reveal any further impairments.
  
  
  CONCLUSIONS
  dPAL and cdPAL performance is hippocampus-dependent in the mouse, but both tasks can be learned in the absence of a functional dHp.
authors.affiliation: Department of Psychology, MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK. chk35@cam.ac.uk.
authors.forename: Chi Hun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Psychology, MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Heath
authors.affiliation: Department of Psychology, MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK.
authors.forename: Brianne A
authors.initials: BA
authors.lastname: Kent
authors.affiliation: Department of Psychology, MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bussey
authors.affiliation: Department of Psychology, MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Saksida
mesh_terms: D000818:Animals; D001331:Automation; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009622:Noise; D010153:Paired-Associate Learning / Q000187:drug effects*; D010775:Photic Stimulation; D011597:Psychomotor Performance / Q000187:drug effects; D012201:Reward
chemical_list: D018755:GABA Agonists; D009118:Muscimol
keywords: Hippocampus; Mouse; Paired-associate learning; Touch screen operant chamber