Abstract
Gene expression related to the formation and modification of memories is regulated epigenetically by chromatin remodeling through histone acetylation. Memory formation and extinction can be enhanced by treatment with inhibitors of histone deacetylases (HDACs). The basolateral amygdala (BLA) is a brain area critically involved in regulating memory for inhibitory avoidance (IA). However, previous studies have not examined the effects of HDAC inhibition in the amygdala on memory for IA. Here we show that infusion of an HDAC inhibitor (HDACi), trichostatin A (TSA), into the BLA, enhanced consolidation of IA memory in rats when given at 1.5, 3, or 6 h posttraining, but not when the drug was infused immediately after training. In addition, intra-BLA administration of TSA immediately after retrieval delayed extinction learning. Moreover, we show that intra-BLA TSA in rats given IA training increased the levels of brain-derived neurotrophic factor in the dorsal hippocampus, but not in the BLA itself. These findings reveal novel aspects of the regulation of fear memory by epigenetic mechanisms in the amygdala.
Highlights
In inhibitory avoidance (IA), a type of fear-motivated conditioning, a new memory is formed after a single training trial, and the behavioral outcome of previously formed memories can be modified upon recall through extinction or reconsolidation
Previous studies have shown that administration of Histone deacetylase (HDAC) inhibitor (HDACi) into the amygdala around the time of training or retrieval resulted in enhanced consolidation and reconsolidation of memory for fear conditioning (Maddox and Schafe, 2011; Monsey et al, 2011), and systemic injections of HDACi could accelerate fear extinction (Lattal et al, 2007; Bredy and Barad, 2008; Itzhak et al, 2012; Stafford et al, 2012)
The present study reveals several novel aspects related to the amygdalar HDAC involvement in fear memory
Summary
In inhibitory avoidance (IA), a type of fear-motivated conditioning, a new memory is formed after a single training trial, and the behavioral outcome of previously formed memories can be modified upon recall through extinction or reconsolidation. These processes are mediated and regulated by a range of neurotransmitter and neuropeptide receptors, intracellular protein kinase signaling pathways, and transcription factors, resulting in changes in gene transcription. Gene expression related to memory consolidation is regulated epigenetically by chromatin remodeling, post-translational DNA modifications, and small RNAs (Levenson and Sweatt, 2005; Barrett and Wood, 2008; Mikaelsson and Miller, 2011; Gräff and Tsai, 2013; Landry et al, 2013). Histone deacetylase (HDAC) proteins deacetylate N-terminal lysine residues in histones, leading to a more compact chromatin structure and reduced gene transcription (Kouzarides, 2007)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
