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Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood

Molecular Psychiatry volume 21, pages 1281–1289 (2016)Cite this article

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Abstract

Critical periods are temporary windows of heightened neural plasticity early in development. For example, fear memories in juvenile rodents are subject to erasure following extinction training, while after closure of this critical period, extinction training only temporarily and weakly suppresses fear memories. Persistence of fear memories is important for survival, but the inability to effectively adapt to the trauma is a characteristic of post-traumatic stress disorder (PTSD). We examined whether Nogo Receptor 1 (NgR1) regulates the plasticity associated with fear extinction. The loss of NgR1 function in adulthood eliminates spontaneous fear recovery and fear renewal, with a restoration of fear reacquisition rate equal to that of naive mice; thus, mimicking the phenotype observed in juvenile rodents. Regional gene disruption demonstrates that NgR1 expression is required in both the basolateral amygdala (BLA) and infralimbic (IL) cortex to prevent fear erasure. NgR1 expression by parvalbumin expressing interneurons is essential for limiting extinction-dependent plasticity. NgR1 gene deletion enhances anatomical changes of inhibitory synapse markers after extinction training. Thus, NgR1 robustly inhibits elimination of fear expression in the adult brain and could serve as a therapeutic target for anxiety disorders, such as PTSD.

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Acknowledgements

SMS is a member of the Kavli Institute for Neuroscience at Yale University. We acknowledge research support from the NIH and the Falk Medical Research Trust to SMS. We thank Adam Kaufman, Stefano Sodi and Yiguang Fu for technical assistance. SMB is supported by the National Science Foundation Graduate Research Fellowship Program.

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Authors and Affiliations

  1. Department of Neurology and Neurobiology, Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven,, CT, USA

    S M Bhagat, S S Butler & S M Strittmatter

  2. Department of Psychiatry and Psychology, Yale University School of Medicine, New Haven,, CT, USA

    J R Taylor

  3. Laboratory of Neuroendocrinology, The Rockefeller University,, New York,, NY, USA

    B S McEwen

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  1. S M Bhagat
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Correspondence to S M Strittmatter.

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Competing interests

SMS is a cofounder of Axerion Therapeutics, seeking to develop PrP- and NgR-based therapeutics.

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Bhagat, S., Butler, S., Taylor, J. et al. Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood. Mol Psychiatry 21, 1281–1289 (2016). https://doi.org/10.1038/mp.2015.179

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