Predator fear memory depends on glucocorticoid receptors and protein synthesis in the basolateral amygdala and ventral hippocampus.

Previous studies have suggested that the basolateral amygdala (BLA) and the ventral hippocampus (VH) are critical sites for predator-related fear memory. Predator exposure is an intense emotional experience and should increase plasmatic corticosterone likely to modulate the emotion-related memories. However, it is unclear whether the BLA and VH harbor plastic events underlying predator-related fear memory storage and how molecular and endocrine mechanisms interact to modulate memory to the predatory threat. Here, we first examined the effects of protein synthesis inhibition in the BLA and VH on fear memory to a predatory threat. We next evaluated how exposure to a predatory threat impacts the corticosterone release and how the inhibition of corticosterone synthesis can influence predator-related fear memory. Finally, we examined how predator exposure triggers the activation of glucocorticoid and mineralocorticoid receptors in the BLA and VH and whether the GR antagonist injection affects predator-related fear memory. We showed that predator-related contextual fear is dependent on protein synthesis in the BLA and VH. Moreover, we described the impact of rapid glucocorticoid release during predatory exposure on the formation of contextual fear responses and that GR-induced signaling facilitates memory consolidation within the BLA and VH. The results are relevant in understanding how life-threatening situations such as a predator encounter impact fear memory storage and open exciting perspectives to investigate GR-induced proteins as targets to deciphering and manipulating aversive memories.

Coordination of escape and spatial navigation circuits orchestrates versatile flight from threats.

Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout. In contrast, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the dorsal premammillary nucleus (PMd) can induce context-specific escape because it projects to escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits is necessary for context-specific escape induced by moderate threats but not panic-related stereotyped escape caused by perceived asphyxiation. Conversely, the PMd projection to the escape-inducing dorsal periaqueductal gray projection is necessary for all tested escapes. Thus, PMd-cck cells control versatile flight, engaging spatial navigation and escape circuits.