Marcelo A Wood
Professor, Neurobiology and Behavior
Chair, Department of Neurobiology and Behavior
|Epigenetics, Long-term Memory, Drug-seeking behavior, Transcription, Histone Acetyltransferases, Histone Deacetylases, Small Molecule Therapeutic|
|URL||Wood lab website|
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 normal long-term memory processes, memories associated with drugs of abuse, and age-related memory impairments.
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.
More recently, the lab has been examining the role of another major epigenetic mechanism, nucleosome remodeling, in synaptic plasticity and memory processes. In particular we are focused on a neuron-specific nucleosome remodeling complex called nBAF. An exciting development in the field is that many of the genes encoding nBAF subunits are mutated in human intellectual disability disorders, including Autism Spectrum Disorder. The lab is working on several subunits, including BAF53b (e.g. Vogel-Ciernia et al., 2013), and their role in memory and drug-seeking behavior.
The regulation of transcription via chromatin modification and nucleosome remodeling falls under epigenetic mechanisms of regulation. One of the alluring aspects of examining epigenetic mechanisms in 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. Thus, epigenetic mechanisms provide a new frontier of neuroscience to help us understand the molecular mechanisms underling many fascinating aspects of how the brain works.
Bieszczad KM, Bechay K, Rusche JR, Jacques V, Kudugunti S, Miao W, Weinberger NM, McGaugh JL, and Wood MA (2015) Histone deacetylase inhibition via RGFP966 releases the brakes on sensory cortical plasticity and the specificity of memory formation. J Neurosci, v35:13124-32.
|Bharadwaj R, Peter C, Jiang Y, Roussos P, Vogel-Ciernia A, Shen E, Mitchell A, Mao W, Whittle C, Dincer A, Jakovcevski M, Pthula V, Rasmussen T, Giakoumaki SG, Bitsios P, Gardner PD, Ernst PA, Ghose S, Sklar P, Haroutunian V, Tamminga C, Myers RH, Futai K, Wood MA, and Akbarian S (2014) Conserved higher order chromatin regulates NMDA receptor gene expression and cognition. Neuron, v84:997-1008.|
|Kwapis, JL and Wood MA (2014) Epignetic mechanisms in fear conditioning: implications for treating post-traumatic stress disorder. Trends in Neurosciences, v37:706-720.|
|Vogel-Ciernia A, Matheos DP, Barrett RM, Kramar E, Azzawi S, Chen Y, Magnan CN, Zeller M, Sylvain A, Haettig J, Jia Y, Tran A, Dang R, Post RJ, Chabrier M, Babayan A, Wu JI, Crabtree GR, Baldi P, Baram TZ, Lynch G, and Wood MA (2013) The Neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory. Nature Neuroscience, v16:552-561.|
|Lattal KM and Wood MA (2013) Epigenetics and persistent memory: Implications for reconsolidation and silent extinction beyond the zero. Nature Neuroscience, v16:124-129.|
|Rogge GA, Singh H, Dang R, and Wood MA (2013) HDAC3 is a negative regulator of cocaine- context associated memory formation. Journal of Neuroscience, v33:6623-6632.|
|Malvaez M, McQuown SC, Rogge GA, Astarabadi M, Jacques V, Carreiro S, Rusche J, and Wood MA (2013) HDAC3 selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. PNAS, v110:2647-52.|
|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.|
|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.|
|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.|
|Grants||NIDA R01 DA025922|
|NIMH R01 MH101491|
|NIDA R01 DA036984|
Society for Neuroscience
Molecular and Cellular Cognition Society
Nu Rho Psi National Honor Society in Neuroscience
Interdepartmental Neuroscience Program
|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|