Marcelo A Wood
Associate Professor, Neurobiology and Behavior
Director, Interdepartmental Neuroscience Program
|Epigenetics, Long-term Memory, Drug-seeking behavior, Transcription, Histone Acetyltransferases, Histone Deacetylases, Small Molecule Therapeutic|
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 has been identified as a pivotal molecular mechanism underlying certain 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 (e.g. McQuown et al., 2011), which we have demonstrated to be a critical negative regulator of long-term memory formation.
The regulation of transcription via chromatin modification falls under epigenetic mechanisms of regulation. One of the alluring aspects of examining chromatin modifications in the role of modulating transcription required for long-term memory processes is that these modifications may provide transient and potentially stable epigenetic marks 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 has 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. Indeed, we have demonstrated that inhibition of HDACs can modulate memory processes in fascinating ways.
For example, we have recently demonstrated that HDAC inhibition can transform a learning event that does not lead to short- or long-term memory into a learning event that now does result in robust long-term memory. HDAC inhibition also generates a form of long-term memory that is persistent and lasts beyond the point at which normal memory fails (e.g. Stefanko et al., 2009). Remarkably, these findings from learning and memory experiments can be applied to drug-seeking behavior. We recently demonstrated that CBP is essential for the formation of cocaine-context associated memories (Malvaez et al., 2011). Conversely, HDAC inhibition can enhance both the rate and extent of extinction of cocaine-context associated memories in a manner that is refractive to reinstatement (Malvaez et al., 2010). We are interested in not only in understanding the basic mechanisms of chromatin modification involved in regulating transcription required for long-term memory processes, but also the development of therapeutic approaches to enhance extinction of fear memories and drug-associated memories.
Malvaez M, Mhillaj E, Matheos DP, Palmery M, and Wood MA (2011) CBP in the nucleus accumbens regulates cocaine-induced histone acetylation and is critical for cocaine-associated behaviors. J Neurosci, v31:16941-8.
McQuown SC, Barrett RM, Matheos DP, Post RJ, Rogge GA, Alenghat T, Mullican SE, Jones
S, Rusche JR, Lazar MA, and Wood MA (2011) HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci, v31:764-774.
|Barrett RM, Malvaez M, Kramar E, Matheos DP, Arrizon A, Cabrera SM, Lynch G, Greene RW, and Wood MA (2011) Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. Neuropsychopharmacology, v36:1545-56.|
|McQuown SC and Wood MA (2011) HDAC3 and the molecular brake pad hypothesis. Neurobio Learning & Memory, v96:27-34.|
|Haettig J, Stefanko DP, Multani ML, Figueroa DX, McQuown SC, and Wood MA. (2011) HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner. Learning & Memory, v18:71-79.|
|Roozendaal B, Hernandez A, Cabrera S, Hagewoud R, Malvaez M, Stefanko D, Haettig J, and Wood MA (2010) Glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification. J Neurosci v30:5037-46.|
|Malvaez M, Sanchis-Segura C, Vo D, Lattal KM, and Wood MA (2010) Modulation of chromatin modification facilitates extinction of cocaine-induced conditioned place preference. Biol Psychiatry, v67:36-43.|
|Stefanko DP, Barrett RM, Ly AR, Reolon GK, and Wood MA (2009) Modulation of long-term memory for object recognition via HDAC inhibition. Proc Natl Acad Sci v106:9447-9452.|
|Barrett RM and Wood MA (2008) Beyond transcription factors: The role of chromatin modifying enzymes in regulating transcription required for memory. Learning & Memory v15:460-467.|
|Lattal KM, Barrett RM, and Wood MA (2007) Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci. v121:1125-1131.|
|Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, and Wood MA (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci. v27:6128-6140.|
Society for Neuroscience
International Behavioral Neuroscience Society
Molecular and Cellular Cognition Society
Nu Rho Psi National Honor Society in Neuroscience
Neurobiology and Behavior
|Research Centers||Center for the Neurobiology of Learning and Memory|
|Institute for Memory Impairments and Neurological Disorders|
|Center for Epigenetics and Metabolism|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=5317|