Long-term memory storage is an essential process to human life. Without long-term memory, we would not be able to remember our pasts, interpret our present, or predict our future. We would have little personal identity and functioning in a world that continues to grow in complexity would be impossible. Our research goal in the Wood lab is to understand the molecular mechanisms underlying long-term memory storage.

Transcriptional activation is thought to be a key process in long-lasting forms of memory and synaptic plasticity. This activation is directed by transcription factors and their coactivators, which regulate gene activation via chromatin remodeling activity or histone covalent modification activity as well as mediating interactions with basal transcription machinery components. One type of histone modification associated with transcriptional activation is acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) that add or remove acetyl groups from histones, respectively. Rubinstein-Taybi Syndrome (RTS), a human developmental disorder characterized by retarded growth and reduced mental function, is caused by deletions, translocations, or point mutations in the CREB-binding protein (CBP) gene. CBP is a transcriptional coactivator that mediates gene expression via direct interactions with the basal transcription machinery as well as its intrinsic HAT activity. Using genetically modified mice, we demonstrated that CBP is critical for hippocampus-dependent long-term memory and hippocampal synaptic plasticity (Wood et al. 2005). To explore the relationship between histone acetylation and memory storage we tested the hypothesis that increasing histone acetylation would enhance memory storage. We found that the histone deacetylase inhibitor trichostatin A increases histone acetylation and enhances memory consolidation for a hippocampus-dependent task and enhances hippocampal synaptic plasticity.

Together, our studies using genetically modified mice and neuropharmacology demonstrate the pivotal role of CBP and histone acetylation in memory and synaptic plasticity and suggest that their exists a layer of transcriptional regulation at the epigenetic level for the expression of genes for long-term memory processes. Further, our studies indicate that histone deacetylase inhibitors are a potential treatment for the cognitive deficits that accompany many psychiatric and neurological disorders such as RTS and Huntington's Disease.

Current projects in the lab center around examining the role of epigenetic regulation of transcription for long-term memory processes using a combined molecular, genetic, and behavioral approach.