Amygdala inhibitory neurons as loci for translation in emotional memories

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 absence of threat, i.e. safety(2–5). Understanding the biological substrates of emotional memories 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 PTSD(5). A key brain area for processing and storing threat memories is the centrolateral amygdala (CeL), which is an important node in the neuronal circuit mediating defensive responses(6–9). Here, we applied intersectional chemogenetic strategies in CeL inhibitory neurons (INs) 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), respectively. We show that de novo translation in CeL Somatostatin-expressing (SOM) INs is necessary for long-term storage of conditioned-threat response whereas de novo translation in CeL protein kinase Cδ (PKCδ)-expressing INs is necessary for conditioned-response inhibition to a safety cue. Our results provide new insight into the role of de novo protein synthesis in distinct CeL inhibitory neuron populations during consolidation of long-term memories.