Inhibition of histone deacetylase 3 via RGFP966 facilitates unusually accurate cue memory for excitatory and inhibitory cue-reward associations
Year: 2018
Type: article
Abstract: Epigenetic mechanisms are key for regulating long-term memory (LTM) and are known to exert control on memory formation in multiple systems of the adult brain, including the sensory cortex. One epigenetic mechanism is chromatin modification by histone acetylation. Blocking the action of histone de-acetylases (HDACs) that normally negatively regulate LTM usually by repressing transcription, has been shown to enable memory formation. Indeed, HDAC inhibition appears to facilitate memory by altering the dynamics of gene expression events for consolidation, however less understood is how molecular-level consolidation processes alter subsequent memory for enhanced storage or retrieval. Here we used a sensory perspective to investigate from a behavioral-level whether the characteristics of memory formed with HDAC inhibitors are different from naturally-formed memory. One possibility is that HDAC-inhibition enables memory to form with greater sensory detail than normal. Because the auditory system undergoes learning-induced remodeling that provides substrates for sound-specific LTM, we aimed to identify behavioral effects of HDAC-inhibition on memory for specific sound features using a standard model of auditory associative cue-reward learning. We found that three systemic post-training treatments of an HDAC3-inhibitor (RGPF966, Abcam Inc.) in rats in the early phase of training facilitated auditory discriminative learning, and increased the specificity for acoustic frequency formed in memory of both excitatory (CS+) and inhibitory (CS-) associations for at least 2 weeks. The findings support that epigenetic mechanisms act on the sensory acuity and precision of memory, which can be revealed by studying the sensory aspects of long-term associative memory formation with HDAC inhibitors.
DOI: 10.7282/t3sx6hfv
Institution: Rutgers, The State University of New Jersey
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2978923859