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 processes and drug-seeking behavior.
It has long been known that transcription is required for a learning event to be encoded into long-term memory. Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification (Barrett and Wood 2008) and remodeling (Vogel-Ciernia and Wood 2014) are two major epigenetic mechanisms that are essential for certain long-term forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Our lab primarily works on the HAT called CBP (e.g. Barrett et al., 2011), which we found to be essential for long-term memory formation, and HDAC3, which we have demonstrated to be a critical negative regulator of long-term memory formation (e.g. McQuown et al., 2011; Kwapis et al., 2018) and drug-seeking behavior (e.g. Rogge et al., 2011; Malvaez et al., 2013).
One of the alluring aspects of examining chromatin modification and remodeling in modulating transcription required for long-term memory processes is that these modifications may provide transient and potentially stable epigenetic changes in the service of activating and/or maintaining transcriptional processes, which in turn may ultimately participate in the molecular mechanisms required for neuronal changes subserving long-lasting changes in behavior. As an epigenetic mechanism of transcription, chromatin modification and remodeling have been shown to maintain cellular memory (e.g. cell fate) and may underlie the strengthening and maintenance of synaptic connections required for long-term changes in behavior (Campbell and Wood, 2019). Indeed, we have demonstrated that inhibition of HDACs can modulate memory processes in fascinating ways (e.g. Stefanko et al., 2009; Malvaez et al., 2013; Lattal and Wood 2013).
Current projects in the lab focus on several epigenetic mechanisms (e.g. histone modification, nucleosome remodeling, DNA methylation) and their role in regulating dynamic and coordinated gene expression profiles required for long-lasting forms of synaptic plasticity, memory, and drug-seeking behavior in the young and aged brain. We use molecular, genetic, viral, pharmacological and behavioral approaches in genetically modified animals and tissue culture. Research in the lab is supported by the National Institute on Drug Abuse, the National Institute on Aging, the National Institute of Mental Health, as well as private foundations and industry partners.
