Amygdala inhibitory neurons as loci for translation in emotional memories

Prerana Shrestha (), Zhe Shan, Maggie Mamcarz, Karen San Agustin Ruiz, Adam T. Zerihoun, Chien-Yu Juan, Pedro M. Herrero-Vidal, Jerry Pelletier, Nathaniel Heintz and Eric Klann ()
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Prerana Shrestha: New York University
Zhe Shan: New York University
Maggie Mamcarz: New York University
Karen San Agustin Ruiz: New York University
Adam T. Zerihoun: New York University
Chien-Yu Juan: New York University
Pedro M. Herrero-Vidal: New York University
Jerry Pelletier: McGill University
Nathaniel Heintz: The Rockefeller University
Eric Klann: New York University

Nature, 2020, vol. 586, issue 7829, 407-411

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2793-8

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