Amygdala inhibitory neurons as loci for translation in emotional memories.

Protein synthesis is required in distinct populations of inhibitory neurons in the mouse amygdala to store memories of danger and safety. To survive in a dynamic environment, animals need to identify and appropriately respond to stimuli that signal danger(1). 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 disorder(5). The centrolateral amygdala is an important node in the neuronal circuit that mediates defensive responses(6-9), 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 2 alpha (p-eIF2 alpha). 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 C delta-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.