Amygdala inhibitory neurons as loci for translation in emotional memories

• Published: 07 October 2020

• Prerana Shrestha, 
• Zhe Shan, 
• Maggie Mamcarz, 
• Karen San Agustin Ruiz, 
• Adam T. Zerihoun, 
• Chien-Yu Juan, 
• Pedro M. Herrero-Vidal, 
• Jerry Pelletier, 
• Nathaniel Heintz & 
• Eric Klann 

Nature volume 586, pages407–411(2020)

Cite this article

• 9183 Accesses
• 223 Altmetric
• Metricsdetails

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)^2,3,4,5. 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 responses^6,7,8,9, 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.

Direct link to the research