Research that boggles the mind

JAX® NOTES Issue 512, Winter 2008

Dr. Zhong-wei Zhang
   Dr. Zhong-wei Zhang
It's no secret that the mammalian brain is by far the most complex organ in all of life. It consists of billions of neurons and trillions of synapses, specialized junctions through which neurons signal to each other and to non-neuronal cells, such as those in muscles or glands. Trying to understand how all these neurons and synapses function
and the consequences when they don't, is a daunting task.

But that has not intimidated Dr. Zhong-wei Zhang, Assistant Professor at The Jackson Laboratory. Since his arrival at JAX in 2006, Dr. Zhang has focused on two related processes: 1) how synapses are remodeled during development, and 2) what role the methyl-CpG binding protein 2 (MeCP2) plays in the development of GABAergic synapses, a major class of inhibitory connections in the brain. Disruptions of these processes have been associated with common brain disorders, such as autism, epilepsy, mood and anxiety disorders, and schizophrenia. Dr. Zhang hopes his research will help scientists develop new and improved treatments for such neural injuries.

Synapse remodeling

Synapse remodeling, the selective elimination and consolidation of synapses during young adulthood, is a little understood but critical step in the development of human behavior. As a study model, Dr. Zhang and his research group are using the whisker sensory relay synapse in the mouse thalamus. They have discovered that extensive remodeling at this synapse occurs early during the mouse's life — and that it can be disrupted by sensory deprivation. Their main objective is to define the cellular and molecular mechanisms involved, thereby providing new insights into the complex interactions between genes and the environment that are critical for the development of the brain and behavior.

MeCP2 and GABAergic transmission

MeCP2 is a key transcriptional repressor in brain development. Mecp2 gene mutations are the primary causes of Rett syndrome, an autism spectrum disorder marked by the loss of voluntary movements and language skills, and one of the most common causes of mental retardation in young girls. Mecp2 mutations also contribute to the pathogenesis of other brain diseases, but the causal mechanisms are poorly understood. Dr. Zhang and his colleagues have found that Mecp2 mutations in mice significantly alter GABAergic transmission. To understand the relationship between MeCP2 and GABAergic transmission, they are using a combination of cellular physiology, molecular biology, and mouse genetics.

Why JAX?

Dr. Zhang was drawn to The Jackson Laboratory by the outstanding scientific environment: "The mice are clearly a great resource, but the Laboratory offers much more. It's the scientific environment here, the opportunity to collaborate with people who are in related fields but have a slightly different perspective, that make it enriching and exciting. The Laboratory has a strong commitment to multi-disciplinary research, and that's very appealing to me."

Dr. Zhang graduated from Peking University, Beijing, China, in 1985. He earned his Ph.D. in Neurophysiology from Université Louis Pasteur in Strasbourg, France, in 1991. From 1991 to 1995, he was a postdoctoral fellow at the University of California, San Diego. In 1995, he moved to Laval University, Québec, Canada, where he worked as a post-doc, research scientist, then assistant professor. He began his work at JAX in the Spring of 2006.