Neural Plasticity, neurodevelopment

Epigenetic Control of Experience-dependent Neural Plasticity
2013 Seed Grant
Zhaolan (Joe) Zhou, Ph.D.
Department of Genetics
University of Pennsylvania

A remarkable feature of brain development and function is that it not only relies on a genomic blueprint, but also depends on sensory experience and the resulting activity communicated within the neural network.  The convergence of genetics and environment lies, at least in part, in the environmentally-affected, experience-dependent gene expression programs that orchestrate experience-dependent neural plasticity in the brain.  The objective of Dr. Zhou’s project is to understand the epigenetic mechanisms by which environment, in the form of experience, interacts with genetics and regulates neural plasticity in the nervous system.  Dr. Zhou hypothesizes that stable yet reversible changes in DNA methylation encode, at least in part, the molecular underpinnings of neural plasticity. He proposes to develop novel transgenic mice to investigate a defined homogenous population of neurons, identify experience-dependent changes in DNA methylation (5mC) genome-wide, and determine the role of DNA methylation in experience-dependent neural plasticity using the paradigm of critical period plasticity in the visual cortex.  With the combined genetic and genomic approaches, Dr. Zhou’s lab hopes to not only advance our understanding of the epigenetic mechanisms underlying experience-dependent neural plasticity, but also provide new insights into the importance of these mechanisms for neurodevelopment, cognitive behavior, and disease.