Histone deacetylase inhibition induces odor preference memory extension and maintains enhanced AMPA receptor expression in the rat pup model

Abstract

Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in neonate rat pups that normally produces only 24-h memory to test behavior and examine receptor protein expression. Our behavioral studies showed that intrabulbar infusion of TSA, prior to pairing of the conditioned stimulus (peppermint odor) with the unconditioned stimulus (tactile stimulation), prolonged 24-h odor preference memory for at least 9 d. The prolonged odor preference memory was selective for the paired odor and was also observed using a specific HDAC6 inhibitor, tubacin, supporting a role for histone acetylation in associative memory. Immunoblot analysis showed that GluA1 receptor membrane expression in the olfactory bulbs of the TSA-treated group was significantly increased at 48 h unlike control rats without TSA. Immunohistochemistry revealed significant increase of GluA1 expression in olfactory bulb glomeruli 5 d after training. These results extend previous evidence for a close relationship between enhanced GluA1 receptor membrane expression and memory expression. Together, these findings provide a new single-trial appetitive model for understanding the support and maintenance of memories of varying duration.

MeBib Suppressed Methamphetamine Self-Administration Response via Inhibition of BDNF/ERK/CREB Signal Pathway in the Hippocampus

“…Furthermore, several studies have shown that HDAC inhibitors regulate glutamate receptor expression. ( Bhattacharya et al ., 2017 ; Xing et al ., 2019 ), however, the molecular mechanisms are poorly understood. We found for the first time MeBib, a HDAC6 inhibitor, suppressed the MA seeking response.…”

Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats

“…Here we chose "odor only" pups as controls since neither odor only or stroking only produces pCREB increases in mitral cells (McLean et al 1999), but the novel peppermint odor would have activated the mitral cells being dissected. Naive pups, pups with stroking only, pups that were subject to training procedures, but did not show behavioral evidence of having learned, and pups given a single odor + stroking trial and a pharmacological manipulation to induce multiple-day memory (Bhattacharya et al 2017) as well as those given training parameters that engage only short-term or intermediate-term memory, which don't depend on transcription, (Grimes et al 2011) will be important comparisons for a fuller understanding the roles of the changes described here.…”