A histone deacetylase inhibitor, trichostatin-A, 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. I hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that might support memory. I used an early odor preference learning model in neonate rat pups to test behavior and examine receptor protein expression. My behavioral studies showed that intrabulbar infusion of TSA, prior to pairing of the conditioned stimulus (peppermint odor) with the unconditioned stimulus (tactile stimulation), prolonged odor preference memory for at least nine days. Western blot analysis showed that GluA1 receptor membrane expression in the olfactory bulbs of TSA-treated pups was significantly increased at 48 h. Immunohistochemistry revealed significant increase of GluA1 expression in olfactory bulb glomeruli five days after training. These results support evidence for a relationship between enhanced GluA1 receptor expression and memory. These findings will permit further exploration of mechanisms which induce and maintain memories.