Absence of fear renewal and functional connections between prefrontal cortex and hippocampus in infant mice

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HIGHLIGHTSAchieving context-independent extinction is critical to enhance exposure therapy.Little is known about the nature of fear memory extinction in the infants.Extinction of fear memory is context-independent in infant mice (P17).IL-BLA connections are functioning while CA1-PFC connections are not in P17 mice.Impairment in fear extinction is widely viewed as a major contributor to, or even an underlying mechanism of, the pathogenesis of anxiety disorders and PTSD. Children with traumatic experience have a higher risk for developing anxiety disorders and PTSD in the adult. Little is known about the nature of fear memory extinction and its underlying mechanism during this period. Here we showed that while renewal of fear memory is context-specific in adult mice, it is absent in infant mice (P17). Using local injection of GABAa receptor antagonist picrotoxin, we found that there is no functional connectivity between infralimbic prefrontal cortex and hippocampus in P17 mice, while prefrontal cortex projection to amygdala is functioning. Hence, the lack of fear renewal is likely caused by the lack of connections between hippocampus and prefrontal cortex which are known to be involved in the regulation of extinction memory.

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