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Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC

Nature Neuroscience volume 13, pages 482–488 (2010)Cite this article

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Abstract

Fear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Cav1.2 Ca2+ channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Cav1.2 channels of the ACC in observational social fear.

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Figure 1: Observational fear learning in the mouse.
Figure 2: Observational fear learning with female mating partners as demonstrators: effect of the duration of co-housing period (familiarity).
Figure 3: The ACC and MITN are involved in observational fear learning.
Figure 4: The ACC is involved in the acquisition of observational fear, but not in memory retrieval of observational fear and in classical fear conditioning.
Figure 5: Synchronized theta activity between the ACC and lateral amygdala during learning of fear by observation.
Figure 6: Cav1.2ACC/Cre mice showed impaired observational fear learning and reduced pain responses.

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Acknowledgements

We thank K. Lee for help with Matlab analysis. This work was supported by the National Honor Scientist program of Korea and the Center of Excellence program from the Korea Institute of Science and Technology.

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Author notes

  1. Daejong Jeon

    Present address: Present address: Department of Neurology, Seoul National University Hospital, Seoul, Korea.,

Authors and Affiliations

  1. Center for Neural Science, Korea Institute of Science and Technology, Seoul, Korea

    Daejong Jeon, Sangwoo Kim, Mattu Chetana & Hee-Sup Shin

  2. Department of Neuroscience, University of Science and Technology, Daejeon, Korea

    Sangwoo Kim & Hee-Sup Shin

  3. ProCell Therapeutics, ProCell R&D Center, Seoul, Korea

    Daewoong Jo

  4. Department of Immunology and Microbiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    H Earl Ruley

  5. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

    Shih-Yao Lin, Dania Rabah & Jean-Pierre Kinet

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Contributions

D. Jeon and H.-S.S. designed the experiments. D. Jeon purified Cre protein. D. Jo and H.E.R. made and provided the vector containing His6-NLS-Cre-MTS. D. Jeon, S.K. and M.C. performed surgeries, microinjections and immunostainings and analyzed the data. D. Jeon and S.K. performed in vivo electrophysiology. S.-Y.L., D.R. and J.-P. K. generated the Cav1.2 conditional mice. D. Jeon and H.-S.S. wrote the manuscript. All of the authors commented on the manuscript.

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Correspondence to Hee-Sup Shin.

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Jeon, D., Kim, S., Chetana, M. et al. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nat Neurosci 13, 482–488 (2010). https://doi.org/10.1038/nn.2504

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