Impaired fear memory extinction during adolescence is accompanied by the depressive-like behaviors

Abstract

Fear is the emotion that is best understood in terms of brain mechanisms. And the management of fear memories is important when facing mental health disorders such as post-traumatic stress. Adolescence is a transitional stage of physical and psychological human development and the ability to deal with the fear memory in adolescence may be a potent factor for developing mental disorders in adulthood. However, little is known about the direct relationship between the ability to deal with the fear memory and appearance of depressive-like behaviors. To assess this, we used a model of associative learning to induce the fear memories and evaluated the depressive-related behaviors in the fear memory extinction process and its underlying cellular mechanisms from adolescent and adult mice. We found that, compared with adult mice, the adolescent mice exhibited impaired fear memory extinction in contextual fear conditioning extinction process. Meanwhile, impaired fear memory extinction was accompanied by more immobility time in forced swimming test, which was used to assess the depressive-like state. Consistent with this, we observed that long-term potentiation (LTP) induction in the hippocampal CA1 region of adolescent mice persistently larger in extinction process in adolescent mice, which was involved the presynaptic mechanism. Together, our results suggest that adolescent mice exhibited a disability to extinct the fear memory, and that this may lead to the depressive-like behaviors via presynaptic-mediated synaptic plasticity. These findings may give us a new insight in the knowledge of some mental disorders caused by persistent unpleasant memories.

Keywords: Depression; Extinction; Fear memory; Long-term potentiation.