title: A translational bridge between mouse and human models of learned safety.
abstract: BACKGROUND
  Learned safety is established by negatively correlating the occurrence of a neutral stimulus and a noxious stimulus, which renders the previously neutral stimulus a 'safety signal'. While the neurophysiological and molecular mechanisms have been characterized in mice, it is currently not known how the neural substrates involved compare between mice and people.
  
  
  METHODS
  Here we attempt to adapt the original animal protocol to humans and use functional magnetic resonance imaging to examine neural responses to the conditioned stimulus in safety conditioned and fear conditioned subjects. Diffusion tensor imaging (DTI) was used in a parallel group of subjects as a first approach to delineate the underlying neural circuitry.
  
  
  RESULTS
  Learned safety is associated with dampened amygdala and increased dorsolateral prefrontal cortex and caudate responses and paralleled by pupillary constriction. A neural connection between the amygdala and the dorsolateral prefrontal cortex is suggested by DTI.
  
  
  CONCLUSIONS
  We present a translational bridge between mouse and human models of learned safety in which cellular and molecular insights from animal experiments are extended to the human neural circuitry. This study provides an example of how animal experiments can be used to inform and target human studies, which in turn can corroborate results obtained in experimental animals.
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY, USA. daniela.pollak@meduniwien.ac.at
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Pollak
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rogan
authors.forename: Tobias
authors.initials: T
authors.lastname: Egner
authors.forename: David L
authors.initials: DL
authors.lastname: Perez
authors.forename: Ted K
authors.initials: TK
authors.lastname: Yanagihara
authors.forename: Joy
authors.initials: J
authors.lastname: Hirsch
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D017397:Prefrontal Cortex / Q000502:physiology*; D011680:Pupil / Q000502:physiology; D057170:Translational Research, Biomedical