Department of Metabolism & Aging
Associate Professor, Department of Neuroscience
Faculty, Graduate Program
Affiliate Research Professor, Dept. of Biological Sciences, Florida Atlantic University
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.
B.S., Biopsychology, University of California, Santa Barbara, 1999
Ph.D., Neurobiology & Behavior, University of California, Irvine, 2005
Faculty of 1000 Selection (2013)
NIDA Young Investigator Award (2005)
Civitan Emerging Scholar Award (2006)
Faculty of 1000 Biology Selection, Exceptional (2007)
NIH/NINDS National Research Scholar Award (2007-2009)
Kauffman Fellow - Program for Venture Education (2008)
Invited Speaker, NIA Epigenomics Roadmap Meeting (2008)
Invited Speaker, NIDA Annual Meeting (2008)
NIH/NIDA Pathways to Independence Award (2009-2014)
Invited Speaker, NIMH Seminar Series (2009)
Young Investigator Award, International Society for Neurochemistry (2009)
Invited Speaker, Keystone Symposium on the Pathophysiology of Autistic Behavior (2010)
Invited Speaker, NIDA Seminar Series (2010)
Faculty of 1000 Biology Selection, Exceptional (2010)
Invited Speaker, Gordon Conference "Epigenetics" (2011)
Invited Speaker, Gordon Conference "Catecholamines" (2011)
Griggs EM, Young EJ, Rumbaugh G, Miller CA. (2013) MicroRNA-182 regulates amygdala-dependent memory formation. Journal of Neuroscience. 2013 Jan 23;33(4):1734-40.
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 maturation of dendritic spine synapses. Cell 2012 Nov 9;151(4):709-23.
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 & Memory. 2011 Dec 14;19(1):9-14. Print 2012 Jan.
Mikaelsson MA, Miller CA. (2011) DNA methylation: a transcriptional mechanism co-opted by the developed mammalian brain? Epigenetics. 2011 May;6(5):548-51. Epub 2011 May 1.
Mikaelsson MA, Miller CA. (2011) The path to epigenetic treatment of memory disorders. Neurobiolgy of Learning and Memory. 2011 Jul;96(1):13-8. Epub 2011 Feb 12. Review.
Rubio MD, Johnson R, Miller CA, Huganir RL, Rumbaugh G. (2011) Regulation of synapse structure and function by distinct myosin II motors. The Journal of Neuroscience. 2011 Jan 26;31(4):1448-60.
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.
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.
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.
Cahill ME, Xie Z, Day M, Barbolina MV, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ and Penzes P. (2009) Kalarin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proceedings of the National Academy of Sciences 106: 13058-63.
Guo X, Hamilton PJ, Reish N, Sweatt JD, Miller CA, and Rumbaugh G (2008) Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of schizophrenia. Neuropsychopharmacology 34: 1659-72.
Miller CA, Campbell SL and Sweatt JD (2008) DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiology of Learning and Memory 89: 599-603.
Miller CA and Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53: 857-69.
Levenson MJ, Roth TL, Lubin FD, Miller CA, Huang IC, Desai P, Malone L, Sweatt JD (2006) Evidence that DNA (Cytosine-5) methyltransferases regulate synaptic plasticity in the hippocampus. Journal of Biological Chemistry 281: 15763-73.
Miller CA and Marshall JF (2005) Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory. Neuron 47: 873-84.
Miller CA and Marshall JF (2005). Altered Fos expression in neural pathways involved in cue-elicited drug seeking. European Journal of Neuroscience 21, 1385-93.
Miller CA and Marshall JF (2004). Altered prelimbic cortex output during cue-elicited drug seeking. Journal of Neuroscience 24, 6889-97.