Involvement of canonical Wnt/?-catenin signaling in the extinction of auditory fear conditioning in male mice

The Wnt signaling pathway plays a critical role in activity-dependent plasticity processes such as long-term potentiation, learning and memory. However, the role of the Wnt signaling pathway in adult extinction is still not well understood. In this study, we aimed to investigate the roles and mechanisms of the canonical Wnt/ beta-catenin signaling pathway in the extinction of auditory fear conditioning (AFC) in adult mice. We found that AFC extinction training induced a significant decrease in p-GSK3 beta and nuclear beta-catenin in the medial prefrontal cortex (mPFC). Micro-infusion of the canonical Wnt inhibitor Dkk1 into the mPFC before AFC extinction training facilitated AFC extinction, suggesting that the Wnt/beta-catenin pathway is involved in AFC extinction. To deter-mine how Dkk1 affects canonical Wnt/beta-catenin signaling in AFC extinction, the protein levels of p-GSK3 beta and beta-catenin were measured. We found that DKK1 produces a decrease in p-GSK3 beta and beta-catenin. Moreover, we found that upregulating the Wnt/beta-catenin pathway using LiCl (2 mu g/side) impaired AFC extinction. These findings may help us understand the role of canonical Wnt signaling pathway in memory extinction and suggest that appropriate manipulating the Wnt/beta-catenin signaling pathway might be a suitable way of therapeutically treating psychiatric disorders.

Automated summary

The Wnt signaling pathway is involved in adult extinction, and manipulating this pathway can facilitate or impair the extinction process. Inhibition of the pathway using Dkk1 accelerates extinction, while enhancement of the pathway impairs extinction. These findings provide insights into the role of the Wnt signaling pathway in memory extinction and suggest its potential therapeutic implications for psychiatric disorders.