Sodium butyrate into the insular cortex during conditioned taste-aversion acquisition delays aversive taste memory extinction

Abstract

Histone acetylation is one mechanism that promotes gene expression, and it increases during learning of various tasks. Specifically, novel taste consumption produces an increased acetylation of histone lysine residues in the insular cortex (IC), where protein synthesis is crucial during memory consolidation of conditioned taste aversion (CTA). However, the role of this elevated histone acetylation during CTA learning has not been examined directly. Thus, the present study investigated the effects of sodium butyrate (NaBu), a histone deacetylase inhibitor, injected into the IC during CTA acquisition. Male Wistar rats, IC bilaterally implanted, were injected 60 min before saccharine presentation, with a total volume of 0.5 µl of NaBu solution (100, 500, and 10 µg/0.5 µl) or saline; 30 min later animals were injected intraperitoneally with lithium chloride, a malaise-inducing drug. The next day, CTA retrieval was tested. No effects of NaBu were observed during acquisition or retrieval, but during extinction trials, a significant delay in aversive memory extinction was observed in the group injected with the lowest NaBu dose. This result indicates that NaBu in the IC strengthens CTA and delays aversive memory extinction, and suggests that histone acetylation could increase long-term taste-aversive memory strength.

Epigenetic mechanisms regulate cue memory underlying discriminative behavior

“…Subsequent studies have expanded on the role of epigenetic mechanisms in the IC – in particular, histone acetylation – to regulate aversive memory for conditioned taste. A 2014 study by Nuñez-Jaramillo and colleagues ( Núñez-Jaramillo et al, 2014 ) found that infusing the general class I HDAC inhibitor, sodium butyrate (NaB), in the IC during CTA strengthened the associative memory between the taste cue and malaise, which was revealed behaviorally as delayed extinction of the taste aversion. The same effect of HDAC inhibition on CTA memory was also reported by ( Rodríguez-Blanco et al, 2019 ) with post-training IC injections of the HDAC1/3-selective inhibitor MS-275 (“entinostat”).…”