Differential Age-dependent Mechanisms of High-frequency Stimulation-induced Potentiation in the Prefrontal Cortex-Basolateral Amygdala Pathway Following Fear Extinction

Post-weaning is a critical period for brain maturation in the rat and is comparable to childhood and adolescences in humans. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) are two brain regions that continue to mature during post-weaning and establish a critical circuit regulating the acquisition and extinction of conditioned fear. We previously demonstrated that exposure to stress leads to significant differences between adults and PWs in the kinetics of extinction behavior as well as differential effects on longterm potentiation. In the current experiments, we aimed to investigate whether prior fear or extinction learning would elicit differences in the ability to induce electrical LTP in the mPFC-BLA pathway in the adult and PW animals. To that end, we subjected adult and PW rats to auditory fear conditioning and extinction, followed by high frequency stimulation (HFS) to induce LTP. The results indicate that when the conditioning protocol is adjusted to produce comparable extinction kinetics in both age groups, no LTP can be induced after fear conditioning in the mPFC-BLA pathway. Importantly, after extinction, LTP was successfully induced, and a significant difference was observed in the levels of potentiation between adults and PW rats. Further, freezing levels during extinction positively correlated with the magnitude of LTP only in adult animals. These results suggest that the changes occurring at the synaptic level following fear extinction are dissimilar in adult and PW animals. Our results further strengthen the assertion that PW and adult fear extinction learning may rely on different mechanisms. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Post-weaning is a critical period for brain maturation in rats, comparable to childhood and adolescence in humans. The basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) continue to mature during this period and play a crucial role in regulating conditioned fear acquisition and extinction. Previous studies have shown that stress exposure leads to differences in extinction behavior and long-term potentiation between adults and post-weaning rats. In this study, the researchers investigated whether fear or extinction learning would affect the ability to induce electrical long-term potentiation (LTP) in the mPFC-BLA pathway in adult and post-weaning animals. The results showed that comparable extinction kinetics were necessary for LTP induction in both age groups, and significant differences in potentiation levels were observed after extinction between adults and post-weaning rats. These findings suggest that synaptic changes following fear extinction are different in adult and post-weaning animals, supporting the notion that fear extinction learning may rely on different mechanisms during these developmental stages.