Amygdala inhibitory neurons as loci for translation in emotional memories

  • Nature. 2020 Oct;586(7829):407-411. doi: 10.1038/s41586-020-2793-8.
Prerana Shrestha  1 ,  Zhe Shan  2 ,  Maggie Mamcarz  2 ,  Karen San Agustin Ruiz  2 ,  Adam T Zerihoun  2 ,  Chien-Yu Juan  2 ,  Pedro M Herrero-Vidal  2 ,  Jerry Pelletier  3 ,  Nathaniel Heintz  4 ,  Eric Klann  5  6
Affiliations
  • 1. Center for Neural Science, New York University, New York, NY, USA. [email protected].
  • 2. Center for Neural Science, New York University, New York, NY, USA.
  • 3. Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • 4. Laboratory of Molecular Biology, The Rockefeller University, New York, NY, USA.
  • 5. Center for Neural Science, New York University, New York, NY, USA. [email protected].
  • 6. NYU Neuroscience Institute, New York University School of Medicine, New York, NY, USA. [email protected].
PMID: 33029009 DOI: 10.1038/s41586-020-2793-8
Abstract

To survive in a dynamic environment, Animals need to identify and appropriately respond to stimuli that signal danger1. Survival also depends on suppressing the threat-response during a stimulus that predicts the absence of threat (safety)2-5. An understanding of the biological substrates of emotional memories during a task in which Animals learn to flexibly execute defensive responses to a threat-predictive cue and a safety cue is critical for developing treatments for memory disorders such as post-traumatic stress disorder5. The centrolateral amygdala is an important node in the neuronal circuit that mediates defensive responses6-9, and a key brain area for processing and storing threat memories. Here we applied intersectional chemogenetic strategies to inhibitory neurons in the centrolateral amygdala of mice to block cell-type-specific translation programs that are sensitive to depletion of eukaryotic initiation factor 4E (eIF4E) and phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). We show that de novo translation in somatostatin-expressing inhibitory neurons in the centrolateral amygdala is necessary for the long-term storage of conditioned-threat responses, whereas de novo translation in protein kinase Cδ-expressing inhibitory neurons in the centrolateral amygdala is necessary for the inhibition of a conditioned response to a safety cue. Our results provide insight into the role of de novo protein synthesis in distinct inhibitory neuron populations in the centrolateral amygdala during the consolidation of long-term memories.

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