CircTmeff-1 in the nucleus accumbens regulates the reconsolidation of cocaine-associated memory

Abstract

Reconsolidation of drug memories is the process of restoring unstable memories after unconditioned (UCS; e.g., drugs) or conditioned stimulus (CS; e.g., drug-paired contexts), and provides promise for prevention of drug relapse. Circular RNAs (circRNAs) have important effects on the transcription and post-transcriptional regulation of gene expression. However, the role of circRNAs in the reconsolidation of drug memories is unclear. Here, we observed that cocaine-induced memory retrieval significantly increased circTmeff-1 level in the nucleus accumbens (NAc) core but not shell. Importantly, the disrupted expression of circTmeff-1 using virus in the NAc core damaged the reconsolidation of cocaine-associated memories. The knockdown of circTmeff-1 in the NAc shell or without UCS retrieval or 9 h after UCS retrieval had no such effects. Mechanistically, using bioinformatic analysis and loss- or gain- of function assays, we revealed that antagomiR-206 reversed the inhibitory effect of circTmeff-1 knockdown on the expression of brain-derived neurotrophic factor (BDNF) during the reconsolidation of cocaine-associated memories. Taken together, these results demonstrate the role of circTmeff-1 in the reconsolidation of cocaine-associated memory and that circTmeff-1 may function as a decoy for miR-206 to regulate the expression of BDNF.

Keywords: BDNF; CircTmeff-1; Cocaine memory reconsolidation; MiR-206; UCS retrieval.