Jesse Gray, Ph.D.

 

Assistant Professor in Genetics

Harvard Medical School
Department of Genetics
New Research Building, Room 0356
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-7667
Fax: 617-432-7595
Email: gray@genetics.med.harvard.edu
Visit my lab page here.




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 not 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. We are approaching this question using primary cultures of mouse cortical neurons, where we control neuronal firing rates using the light-activated ion channel Channelrhodopsin. A particular area of focus is on interrogating neuronal activity-regulated genomic DNA elements (e.g., enhancers) functionally, using a massively parallel high-throughput screening approach.

Second, 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. One key step will be to use transcriptional activation to label specific neurons that are activated during memory acquisition and whose newly formed connections store a “memory trace.” This approach will be facilitated by the fact that robust long-term memories can be formed in single training sessions in behavioral paradigms such as auditory fear conditioning.


For a complete listing of publications click here.



Last Update: 11/7/2013