Assistant Professor of Genetics
Harvard Medical School
New Research Bldg. 0356
77 Ave Louis Pasteur
Boston, MA 02115
Animal genomes endow cells and circuits with the ability to form life-long memories. How does a genome orchestrate this dynamic interaction of neurons with experience? The genome responds to experience by unleashing bursts of new gene expression that rewire circuits to store long-term memories. These bursts of gene expression rely on an exceedingly complicated network of neuronal activity-regulated transcription factors. It is neither known why such an extensive network is necessary nor how it works. We are taking a two-pronged approach to understand how this transcriptional network rewires neuronal circuits. First, we are applying recently developed genomics and systems biology approaches to understand how the activity-regulated transcriptional network responds to increases in neuronal firing rates. At the same time, we are establishing brain slice and in vivo experimental systems in which we can manipulate the transcriptional network in an intact circuit, using electrophysiological, optogenetic, and behavioral tools to assess how these manipulations affect neuronal circuit rewiring.
Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley
PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010 May 13;465(7295):182-7. PMCID: PMC3020079.
Flavell SW, Kim TK, Gray JM, Harmin DA, Hemberg M, Hong EJ, Markenscoff-Papadimitriou E, Bear DM, Greenberg ME. Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron. 2008 Dec 26;60(6):1022-38. PMCID: PMC2630178.