Work

Extinction of contextual fear memory is facilitated in TRPM2 knockout mice

Year: 2025

Type: article

Abstract: Transient receptor potential melastatin type 2 (TRPM2) is a nonselective cation channel involved in synaptic plasticity. We investigated its role in contextual fear conditioning and extinction of conditioned fear using Trpm2-deficient (Trpm2 −/− ) mice. Trpm2 −/− mice exhibited reduced acquisition of contextual fear memory during conditioning but had an intact freezing response to conditioning context 24 h after conditioning. They also showed a reduced freezing response to extinction training, indicating facilitated extinction. Consistent with this, infusion of flufenamic acid (FFA), a TRPM2 antagonist, into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. The enhanced extinction in Trpm2 −/− and FFA-treated mice was associated with down-regulation of immediate-early genes (IEGs) including Npas4, c-Fos, Arc and Egr1 in the hippocampus after extinction training. Our results indicate that TRPM2 plays a positive role in retention of contextual fear memory by modulating neuronal activity in the hippocampus, and suggest that TRPM2 activity could potentially be targeted to strengthen extinction-based exposure therapies for post-traumatic stress disorder (PTSD).

Source: Molecular Brain

DOI: 10.1186/s13041-025-01181-2

Authors: Seung Yeon Ko, Do Gyeong Kim, Huiju Lee, Sung Jun Jung, Hyeon Son

Institution: Hanyang University

Language: English

Topic: Memory and Neural Mechanisms

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,890