Courtney Miller, Ph.D.
Ph.D., Neurobiology & Behavior and Center for the Neurobiology of Learning & Memory (2005), University of California, Irvine, California
Department of Neuroscience
130 Scripps Way C349
Jupiter, Florida 33458
Our laboratory is working to understand the neurobiological underpinnings of memory disorders, with the goal of developing novel therapeutics.
Our research focuses on the contribution of epigenetic mechanisms to two serious health issues, drug addiction and age-related memory decline. Interestingly, while addiction and mild cognitive impairment represent opposing disorders of memory, both are aberrations of a normal cognitive process. The neurochemical alterations produced by a drug of abuse, such as cocaine, initiate a cascade of events that produce aberrantly strong memories. On the other hand, the poorly understood events of aging result in weakened memory traces. This bidirectionality demonstrates that memories are susceptible to modulation by any number of processes capable of influencing the CNS.
Thus, we believe that by understanding the dynamic and stable nature of epigenetic mechanisms in the brain, along with their transcriptional consequences, we can better our understanding of the memory processes we take for granted every day. For example, how does a dynamic brain stably maintain memories beyond the initial functional and structural changes? How can we speed up the process of extinguishing a memory in addicted individuals, while preventing this from happening in older adults? How does the brain update memories? We are working to address these questions using a variety of animal behavioral models in combination with techniques ranging from viral delivery of shRNAs in vivo to bisulfite pyrosequencing for visualizing specific changes in cytosine methylation.
Miller CA and Marshall JF (2005) Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory. Neuron 47, 873-84.
Miller CA, Sweatt JD. (2006) Amnesia or retrieval deficit? Implacations of a molecular approach to the question of reconsolidation. Learning and Memory 13, 498-505.
Miller CA and Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53, 857-69.
Kilgore M*, Miller CA*, Fass DM, Hennig KM, Haggerty S, Sweatt JD and Rumbaugh G (2010). Inhibitors of Class I histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s Disease. Neuropsychopharmacology 35, 870-80.
Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR, Rivera IM, Rubio MD, Rumbaugh G and Sweatt JD (2010) Cortical DNA methylation maintains remote memory. Nature Neuroscience 13, 664-6.
Rex C, Gavin CF, Rubio MD, Kramar EA, Jia Y, Huganir RL, Muzyczka N, Gall CM, Miller CA, Lynch G and Rumbaugh G (2010) Myosin IIB regulates actin dynamics during synaptic plasticity and memory formation. Neuron 67, 603-17.
Gavin CF, Rubio MD, Young E, Miller C, Rumbaugh G. (2011) Myosin II motor activity in the lateral amygdala is required for fear memory consolidation. Learning and Memory 19, 9-14.
Mikaelsson MA, Miller CA. (2011) The path to epigenetic treatment of memory disorders. Neurobiology of Learning and Memory, 96, 13-8.
Clement JP, Aceti M, Creson TK, Ozkan ED, Shi Y, Reish NJ, Almonte AG, Miller BH, Wiltgen BJ, Miller CA, Xu X, Rumbaugh G. (2012) Pathogenic SYNGAP1 mutations impair cognitive development by disrupting the maturation of dendritic spine synapses. Cell 151, 709-23.
Griggs EM, Young EJ, Rumbaugh G, Miller CA. (2013) MicroRNA-182 regulates amygdala-depedent memory formation. Journal of Neuroscience 33, 1734-1740.
Awards, Recognition, Appointments, and Honors
2005 NIDA Young Investigator Award
2006 Civitan Emerging Scholar Award
2007 Faculty of 1000 Biology Selection, Exceptional
2007-09 NIH/NINDS National Research Scholar Award
2008 Kauffman Fellow - Program for Venture Education
2008 Invited Speaker, NIA Epigenomics Roadmap Meeting
2008 Invited Speaker, NIDA Annual Meeting
2009-14 NIH/NIDA Pathways to Independence Award
2009 Invited Speaker, NIMH Seminar Series
2009 Young Investigator Award, International Society for Neurochemistry
2010 Invited Speaker, NIDA Seminar Series
2010 Invited Speaker, Keystone Symposium on the Pathophysiology of Autistic Behavior
2010 Faculty of 1000 Biology Selection, Exceptional
2011 Invited Speaker, Gordon Conference "Epigenetics"
2013 Faculty of 1000 Selection