A translational bridge between mouse and human models of learned safety.
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.
Pollak
Daniela D
DD
Department of Neuroscience, Columbia University, New York, NY, USA. daniela.pollak@meduniwien.ac.at
Rogan
Michael T
MT
Egner
Tobias
T
Perez
David L
DL
Yanagihara
Ted K
TK
Hirsch
Joy
J
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